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| DRUGS (LICENSING, REGISTERING AND ADVERTISING) RULES, 1976 | |
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2. Definitions.-- In these rules, unless there is anything repugnant in the subject or context:-- (a) "active pharmaceutical ingredient" means a substance or compound that is intended to be used in the manufacture of a pharmaceutical product as a pharmacologically active compound (ingredient); (b) "airlock" means an enclosed space with two or more doors, which is interposed between two or more rooms of differing classes of cleanliness for the purpose of controlling the airflow between those rooms when they need to be entered and an airlock is designed for and used by either people or goods; (c) "authorized person" means a person responsible for the release of batches of product for sale; (d) "basic manufacture" means manufacture of a drug from basic raw material to a product which is ready for use as a starting material for the formulation of a finished drug or for repacking and such manufacture may involve chemical, bio-chemical, photochemical, microbial or such other processes or a combination of any of such processes; (e) "batch (or lot)" means a defined quantity of starting material, packaging material, or finish product processed in a single process or series of processes so that it could be expected to be homogeneous in the case of continuous manufacture the batch must correspond to a defined fraction of the production, characterized by its intended homogeneity, and to complete certain stages of manufacture it may sometimes be necessary to divide a batch into a number of sub-batches, which are later brought together to from a final homogeneous batch; (f) "batch number (or lot number)" means a distinctive combination of numbers and or letters which specifically identifies a batch on the labels, the batch records, the certificates of analysis, and that permit the production history of the batch to be traced and revived. (g) "batch numbering system" means a standard operating procedure describing the details of the batch numbering; (h) "batch records" means all documents associated with the manufacture of a batch of bulk product or finished product showing a history of each batch of product and of all circumstances pertinent to the quality of the final product; (i) "biological agents" means micro-organisms, including genetically engineered micro-organisms, cell cultures and endoparasites, whether pathogenic or not; (j) "bulk product" means any product that has completed all processing stages up to, but not including, final packaging; (k) "calibration" means the set of operations that establish, under specified conditions, the relationship between values indicated by a instrument or measuring system for especially weighing, recording and controlling, or the values represented by a material measure and the corresponding known values of a reference standard and the limits for acceptance of the results of measuring; (l) "clean area" means an area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce and or eliminate introduction, generation and retention of contaminants within the area; (m) "compounding" means scientific combination of two or more ingredients with a view to make a finished drug; (n) "consignment or delivery" means the quantity of starting material or of a drug product, made by one manufacturer and supplied one time in response to a particular request or order, a consignment may comprise one or more packages or containers and may include material belonging to more than one batch; (o) "critical process" means a process that may cause variation in the quality of the pharmaceutical product; (p) "cross-contamination" means contamination of a staring material intermediate product, or finished product with another starting material or drug during production; (q) "finished product" means a product that has undergone all stages of production, including packaging in its final container and labeling; (r) "Form" means a form set forth in Schedule A; (s) "formulation" means all operations involved in converting a drug into a final pharmaceutical dosage form ready for use as a finished drug including compounding, processing, formulating, filling, packing, finishing, labelling and other like processes; (t) "good manufacturing practices for pharmaceutical products"
means part of quality assurance which:-- (u) "half-finished product" means any material or mixture of materials that has to undergo further manufacture; (v) "in-process control" means checks performed during production in order to monitor and if necessary to adjust the process to ensure that the product conforms to its specifications and control of the environment or equipment may also be regarded as a part of in-process control; (w) "intermediate product" means partly processed material that must undergo further manufacturing steps before it becomes a bulk product; (x) "large-volume parenterals" means sterile solutions intended for parenteral application with a volume of more than 100ml in one container of the finished dosage form; (y) "manufacture" means all operations of production, quality control, release, storage and the related controls; (z) "manufacturer" means a company that carries out at least one step of manufacture; (aa) "marketing authorization" means a document, issued by the Drug Registration Board set up under the Drugs Act, 1976, as a certificate of drug registration; (ab) "master formula" means a document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedure and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the in-process controls; (ac) "master record" means a document or set of documents that serve as a basis for the batch documentation (blank batch record); (ad) "new drug" means a drug that has not been commonly sold or distributed to the public in Pakistan and is introduced for the first time; (ae) "Ordinance" means the Drugs Ordinance, 1976 (IV of 1976); (af) "packaging" means all operations, including filling and labelling which a bulk drug has to undergo in order to become a finished product; Note: Sterile filling would not normally be regarded as part of packaging, the bulk product being the filled, but not the finally packaged, primary container. (ag) "packaging material" means any material, including printed material, employed in the packaging of a pharmaceutical product, excluding any outer packaging used for transportation or shipment and packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product; (ah) "pharmaceutical product" means any drug intended for human use or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form; (ai) "processing instructions or procedures" means a defined in clause (ab) of this section; (aj) "production" means all operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing and packaging, to its completion as the finished product; (ak) "purity" means the degree to which other chemical or biological entities are present in any substance; (al) "quality assurance" means the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use and so incorporates good manufacturing practices, Quality Control and other factors including product design and development and good laboratory practices; (am) "quality control" means the part of good manufacturing practices concerned with sampling, specifications, and testing as well as the organization, documentation, and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor finished products released for sale or supply until their quality has been judged to be satisfactory and it is involved in all decisions concerning the quality of the product; (an) "quarantine" means status of starting or packaging materials intermediate, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection, or reprocessing; (ao) "reconciliation" means a comparison, making due allowance for normal variation between the amount of product or materials theoretically produced or used and the amount actually produced or used; (ap) "recovery or blending" means the introduction of all or part of previous batches, or of redistilled solvents and similar products, of the required quality into another batch at a defined stage of manufacture; (aq) "repacking" means all operations involved in the transfer of a drug from a larger container or packing into smaller containers or packings including filling, packing and labeling with a view to make it ready for retail sale or wholesale, but does not includes any compounding, or processing with a view to formulate it in any dosage form; (ar) "retail sale" means a sale other than wholesale; (as) "reprocessing" means the reworking of all or part of a batch of product of an unacceptable quality from a refined stage of production so that its quality may be rendered acceptable by one or more additional operations; (at) "returned product" means finished product sent back to the manufacturer or distributor; (au) "Schedule" means Schedule to these rules; (av) "semi-basic manufacture" means manufacture from an intermediate substance of a drug to be used as a starting material for the formulation of a finished drug or to be used for repacking; (aw) "specification" means the requirements with which the products or materials used or obtained during manufacture must conform as specified in the Drugs (Specification) Rules, 1978; (ax) "standard operating procedure" means an authorized written procedure indicating instructions for performing operations not necessarily specific to a given product or material but of a more general nature such as equipment operation, maintenance and cleaning validation, cleaning of premises and environmental control sampling and inspection, and certain standard operating procedures may be used to supplement product specific master and batch production documentation; (ay) "starting material" means any substance used in the production of a pharmaceutical product but excluding packaging materials; (az) "system" means a regulated pattern of interacting activities and techniques which are united to form an organized whole; (ba) "validation" means the documented act of proving that any procedure, process, equipment, material, activity or system works correctly and actually leads to the expected result; and (bb) "wholesale" means sale to a person who purchases
for the purpose of selling again and includes sale to a hospital
or dispensary, or to medical, educational or research institute. 4. Manufacture on more than one set of premises: If drugs are manufactured on more than one set of premises, a separate application shall be made and a separate licence shall be issued in respect of each such set of premises. 5. Application for licence to manufacture drugs and fee therefor: (1) An application for the grant or renewal of a licence referred to in clauses (i) to (iv) of rule 3 shall be made in Form 1 or l-A to the Central Licensing Board addressed to its Secretary. (2) An application under sub-rule (1) shall be accompanied by the proper fee as specified in Schedule F. Proviso: Added vide S.R.O. 536(1)/93 dated 23rd June 1993. Omitted vide S.R.O. 277 (1)/96 dated 2 lst April 1996. (3) If the application for renewal of the licence is made after the expiry of the period of the validity of the licence, it shall be treated as a fresh application for the grant of a licence. (4) A fee of rupees one hundred shall be paid for a duplicate copy of the licence if the original is defaced, damaged or lost. Such copy of the licence shall bear the words "DUPLICATE COPY". (5) Any fee deposited under sub-rule (2) Shall in no case be refunded. 6. Duration of a licence to manufacture drugs: A licence issued under this Chapter shall, unless earlier suspended or cancelled, be inforce for a period of five years from the date of issue and may thereafter be renewed for periods of five years at a time: Provided that an application for renewal shall not be entertained unless it has been made within sixty days after the expiry of the licence and when an application has been made as aforesaid the licence shall subject to the orders passed on the application for renewal continue in force for the next period of two years. Provided further that duration of a licence issued under rule 21 shall be two years unless earlier suspended or cancelled. 7. Certificate of licence to manufacture drugs: A licence to manufacture by way of basic manufacture, semi-basic manufacture, formulation or repacking, as the case may be, shall be issued in Form 2. . 8. Central Licensing Board: (1) The Central Licensing Board shall consist of the following members, namely :-- (a) the Director-General Health, Government of Pakistan, who shall
be its ex-officio Chairman; (2) No person who is a member of the Appellate Board shall be nominated to the Central Licensing Board. (3) The members of the Central licensing Board, other than its ex officio members, shall hold office for three years and shall be eligible for renomination. (4) The Central Licensing Board may co-opt any other person who is expert in the pharmaceutical or medical profession for advice on any particular matter under consideration. (5) The meetings of the Central Licensing Board may be held at such time as the Board may deem fit and, on the request of any of its members, the Chairman may at any time call a meeting if there is any important matter for its consideration. (6) In the absence of the Chairman, the Board may elect one of its members to preside over a meeting. (6-A) The quorum to constitute a meeting of the Board shall be one third of its total membership. (7) The Central Licensing Board may authorise the Chairman to any of its members to perform any specific function of the Board for a specified period. (8) The Central Licensing Board shall follow such policy directing as the Federal Government may issue from time to time. (9) No act or proceeding of the Central Licensing Board shall be invalid merely on the ground of the existence of any vacancy in, or any defect in the constitution of the Board. (10) The chairman and the Secretary of the Central Licensing Board shall, after the Board has approved the issuance of a licence sign the licence. (11) Subject to rule 14, the Central Licensing Board may appoint a licensing authority or authorities for such purpose as it may deem fit. 9. Powers of the Central Licensing Board: (1) The members of the Central Licensing Board shall exercise all the powers of an Inspector without restriction as to area, and shall have the powers of a Provincial Inspector in relation to Section 30. (2) In the exercise of their powers the members of the Central Licensing Board shall follow the procedure prescribed for the Federal Inspector - Provided that member nominated by a Provincial Government may follow the procedure as laid down for a Provincial Inspector. 10. Procedure of Central Licensing Board: (1) The Central Licensing Board may, before issuing a licence, cause the premises in which the manufacture is proposed to be conducted to be inspected by itself or by its sub-committee or by a panel of Inspector or experts appointed by it for the purpose, which may examine all portions of the premises and the plant and appliances, inspect the process of manufacture intended to be employed and the means to be employed for standarizing, if necessary, and analysing substances to be manufactured and enquire into the professional qualifications of the technical staff employed. (2) Where inspection under sub-rule (1) is carried out by a sub-commmittee or panel of experts of Inspectors appointed under the said sub-rule it shall forward to the Central Licensing Board a detailed report of the result of the inspection. (3) If the Central Licensing Board, after' such further enquiry, if any, as it may consider necessary, is satisfied that the requirements of the rules have been complied with, it may issue a licence in Form 2. (4) If the Central Licensing Board is not so satisfied, it shall reject the application and shall inform the applicant of the reasons for such rejection and of the conditions which must be satisfied before a licence may be issued. (5) No application shall be entertained within three months of the rejection of an application under sub-rule (4). (6) If after the expiry of three months but within six months of the rejection of an application under sub-rule (4), the applicant informs the Central Licensing Board that the requirements of the rules have been fulfilled, the Board may if after causing a further inspection to be made, is satisfied that the conditions for the grant of a licence have been complied with, issue a licence and no further fee shall be required to be deposited for such an application. (7) In case an application for licence to manufacture is made after the expiry of six months from the date of rejection of an application under sub-rule (1), such application shall be treated as a fresh application and full fee shall have to be deposited. 11. Special provisions regarding grant of a licence: (1) Where a manufacturer intends to manufacture a drug a part of the process of which is of specialised nature and would be uneconomical for him to conduct it, the Central Licensing Board may permit such process to be undertaken at another licensed premises specialised for this purpose, subject to such conditions, if any, as may be specified in this behalf. (2) If a person is conducting a part of the process of the manufacture on behalf of another manufacturer in accordance with the permission granted under sub-rule (1), and he is not responsible for the quality of the final product, the Central Licensing Board may not require him to establish an independent quality control laboratory for such products. (3) If a person possesses, or applies for, more than one type of licences to manufacture drugs in the same premises, he may establish one Quality Control Department for the purpose of both the licences. 12. Cancellation or suspension of licences: (1) If licensee does not comply with any of the conditions of a licence or violates any of the provisions of the Ordinance or the rules, or fails to deposit the requisite amount of the Central Research Fund due from him, the Central Licensing Board may, by an order in writing stating the reasons thereof, cancel a licence or suspend it for such period as it thinks fit, either wholly or in respect of some of the drugs to which it relates. (2) The Central Licensing Board shall, before cancelling or suspending a licence under sub-rule (1), provide an opportunity of being heard to the licensee. (3) When a licence is cancelled or suspended, an entry to that effect shall be recorded on the licence. (4) A licensee whose licence has been cancelled or suspended may appeal to the Appellate Board within sixty days of the date of receipt of the decision of the Central Licensing Board by the licensee and until the Appellate Board has given its order, the licence shall remain cancelled or suspended, as the case may be. 13. Renewal of a licence: On application being made for renewal, the Central Licensing Board may cause an inspection to be made, and if satisfied that the conditions of the licence and the rules are and will continue to be observed, shall issue a certificate of renewal or otherwise reject the application and inform the licencee accordingly. 14. Licensing authority: For the purpose of Section 18 of the Ordinance the Secretary to the Government of Province in the Health Department shall be the licensing authority for that Province. 15. Conditions for grant or renewal of a licence to manufacture drugs by way of basic or semi-basic manufacture: (1) Before a licence to manufacture by way of basic or semi-basic manufacture is granted or rehewed, the Central Licensing Board shall satisfy itself that the following conditions are complied with by the applicant, namely :-- (a) The applicant shall provide premises which shall be suitable for intended use, in size and construction and shall be located in an area free from offensive and obnoxious odours and other possible sources of contamination. (b) The applicant shall provide adequate space, plant and equipment for the manufacturing operations; (c) The manufacture shall be conducted under the active directions and personal supervision of competent technical staff consisting of. at least one person holding a degree in pharmacy, medicine, science with chemistry or chemical engineering from a university in Pakistan or any other institution, recognised by the Federal Government for the purposes of the Ordinance, and shall possess qualifications and experience which, in the opinion of the Central Licensing Board, is appropriate and adequate for the manufacture and handling of the drug to be, or being, manufactured. (d) The applicant shall establish an independent Quality Control Department and maintain separate staff, premises and adequate laboratory equipment for carrying out tests of the strength, potency, quality and purity of the substances being or to be used in the manufacture. (e) The Quality Control Department shall be independent of the manufacturing units and its incharge shall be a whole-time employee of the manufacturer and shall possess a degree in pharmacy, or a degree in science with chemistry, or a degree in medicine, microbiology, pharmacology, or bacteriology from a university in Pakistan or any other institution recognised by the Federal Government for the purposes of Ordinance, as the Central Licensing Board may deem fit for any particular unit; and shall be independent of the incharge of the manufacture (Production Units). (f) the applicant shall ensure that-- (i) the manufacturing premises shall be maintained properly and
shall, as far as possible, be orderly , clean and free from accumulated
waste and vermin; (g) The applicant shall provide-- Provided that where a person possess or applies for a licence to manufacture by way of basic and he also intends to conduct semi-basic manufacture of drugs, he may conduct such manufacture under the same license, subject to the approval of, and under such conditions as, the Central Licensing Board may specify, and 16. Conditions for the grant or renewal of licence to manufacture drugs by way of formulation: Before a licence to manufacture drugs by way of formulation is granted or renewed, the Central Licensing Board shall satisfy itself that the following conditions are being complied with by the applicant namely :-- (a) The factory premises shall comply with the conditions specified
in Schedule B. (bb) An applicant for registration of insecticides, pesticides and household disinfectants shall, in addition to the conditions specified in Schedule B and Schedule B-l, comply with the conditions specified in Schedule B-l, A. (c) The manufacture shall be conducted under the 'active directions and personal supervisions of competent technical staff conisting of at least one person who is a whole-time employee and who has-- (i) a degree in Pharmacy from a university in Pakistan or any other institution recognised by the Federal Government for the purpose of the Ordinance and has at least twelve months of practical experience in the manufacture of drugs; or (ii) a degree in science with chemistry or pharmaceutical chemistry as the principal subject who, for the time being is working as incharge of a licensed pharmaceutical manufacturing unit, has not less than ten years practical experience in the manufacture of drugs intended to be manufactured knowledge of pharmacy which, in the opinion of the Central Licensing Board is adequate for the purposes; or (iii) any foreign qualification the quality and content of the training of which are comparable with those described in sub-clause (i) or sub-clause (ii) and is approved for the purposes, of this sub-rule by the Central Licensing Board: Provided that the Central Licensing Board may, in the case of manufacture of drugs included in Schedule C, permit the manufacture of such drugs under the active direction and personal supervision or a person holding a degree in medicine or veterinary sciences of a university in Pakistan or any other institution recognised by the Federal Government, with at least three years experience in the manufacture, testing and analysis of biological products which are intended to be produced: Provided further that the Central Licensing Board, may, in the case of anufacture of disinfectant fluids, insecticides liquid paraffin, medicinal gases, non-chemical contraceptives, plaster of paris, surgical dressing or chemicals for the manufacture of which the knowledge of pharmacy or pharmaceutical chemistry is not essential, permit manufacture of the drug under the active direction and personal supervision of competent staff who, […..] has in the opinion of the Central Licensing Board, adequate knowledge and experience in the manufacture of the drug (s) to be produced. (d) The applicant shall establish an independent Quality Control Department and maintain separate staff, premises and adequate laboratory equipment for carrying out tests of strength, quality and purity of the substances being or to be used in the manufacture. Provided further that a person already approved by the Central Licensing Board as the production incharge of a pharmaceutical firm shall continue to be the technical supervisor of that firm for the purposes of this rule. (e) The Quality Control Department shall be independent of the manufacturing unit and its incharge shall be whole time employee of the manufacturer and shall possess a degree in pharmacy, or a degree in science with chemistry or a degree in medicine or pharmacology (for pharmacological testing) or a degree in microbiology (for microbiological testing) and has sufficient experience in testing of drugs: Provided that in the case of drugs specified in Schedule C, the Central Licensing Board may allow the applicant to make arrangements with some other institution approved by the Central Licensing Board for such tests to be regularly carried out on his behalf by that institution. 17. Licence to manufacture drugs by way of repacking: (1) A licence to manufacture drugs by way of repacking is required for the repacking of such drugs, and under such conditions, as are specified in Schedule D. (2) Where a person possesses or applies for a licence to manufacture by way of formulation and he also intends to conduct repacking of drugs, he may conduct such repacking under the same licence subject to the approval of, and under such conditions as, the Central Licensing Board may specify. 18. Condition for the grant or renewal of a licence to manufacture drugs by way of repacking: Before a licence to manufacture drugs by way of repacking is granted or renewed, the Central Licensing Board shall satisfy itself that the following conditions are complied with by the applicant, namely :-- (a) adequate space and equipment shall be provided; 19. Conditions of licence to manufacture, by way of basic manufacture, semi-basic manufacture formulation and repacking of drugs: (1) A licence to manufacture by way of basic, semi-basic manufacture, formulation or repacking of drugs shall be subject to the conditions stated herein, if any, and to the further condition that the licensee shall continue to maintain conditions on the basis of which he was granted a licence. (2) The licence shall be kept on the licenced premises and shall be produced at the request of any member of the Central Licensing Board or of Provincial Quality Control Board or an Inspector. (3) Any change in the expert staff or significant alteration in the licensed premises or equipment shall be immediately notified to the Central Licensing Board. (4) The licensee shall maintain in the inspection book provided by the Central Licensing Board at the time of the issuance of the licence on which a member of the said Board or of a Provincial Quality Control Board or an Inspector shall record proceedings of each of his visits, his impressions and the defect or irregularities noticed, if any, by him and such inspection book shall be signed by him as well as the licensee or his authorised agent. (5) If any defects or irregularities are recorded in the inspection
book under sub-rule (4) the manufacturer shall take steps to remove
such defects or irregularities. (7) The licensee shall comply with the provisions of the Ordinance and the rules and with such further requirements, if any, as may be specified in any rule subsequently made-in this behalf or any other condition that may be imposed at the time of grant of a licence in the special circumstances of each case. (8) The licensee shall allow any member of the Central Licensing Board or of a Provincial Quality Control Board or an Inspector to enter, with or without prior notice, any premises and to inspect the plant and the process of manufacture & the means employed in standardising and testing the drugs and to take samples for test and analysis. (9) The licensee shall allow any member of the Central Licensing "Board or of a Provincial Quality Control Board of an Inspector to inspect all registers and records maintained under these rules and to take samples of the manufactured drugs and shall supply to such member or Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Ordinance and the rules have been observed. (10) The Licensee shall, on demand, furnish to the Central Licensing Board or the Provincial Quality Control Board or to such authority as the Central Licensing Board may direct, from every batch of a drug, or from such batch or batches of drugs as it may from time to time specify, a sample for examination and, if required, furnish full Protocols of the tests which have been applied. (11) If the Central Licensing Board or a Provincial Quality Control Board so directs, the licensee shall not sell or offer for sale any batch of a drug in respect of which a sample is, or protocols are, furnished under clause (10) until a certificate authorising the sale of the batch of such drug has been issued to him by or on behalf of the Central Licensing Board or the Provincial Quality Control Board, as the case may be. (12) The licensee shall on being informed by the Central Licensing Board or a Provincial Quality Control Board that any part of any batch of a drug has been found not to conform with the requirements of the Ordinance or the rules and on being directed so to do, withdraw the remainder of the batch of such drug from sale and, so far as may in the particular circumstances of the case be practicable, recall all issues already made from that batch and dispose it of in such manner as may be directed by the said Board. (13) No drug manufactured under licence shall be sold unless the
precautions necessary for preserving its properties have been observed
throughout the period after manufacture. (14) The Licensee shall , by the 30th June and the 31st December each year, Whichever is immediately after the annual financial closing of the company. contribute one per cent of his gross profit before deduction of income-tax towards the Central Research Fund to be maintained by the Federal Government and utilised by it in accordance with the Drugs (Research) Rules, 1978: Provided that the Central Licensing Board may allow a portion of
such contribution to be spent by the firm itself for research and
development of new drugs or for establishing research laboratories
when it is fully satisfied that such expenditure will be utilised
for the said purpose effectively and properly. (14-A) The contributions made towards the Central 'Research Fund
under sub-rule (14) shall be kept in such bank as the Federal Government
may specify and shall be utilised in accordance with the Drugs (Research)
Rules, 1978. 20. Additional conditions of licence to manufacture drugs by way of formulation: A licence to manufacture drugs by way of formulation shall, in addition to the conditions laid down in rule 19, be subject to the following further conditions, namely :-- (a) The licensee shall comply with the requirements and the conditions in respect of goods practices in the manufacture and quality control of drug; as specified in Schedule B-II. (b) The licensee shall record in Schedule B-Ill the particulars of manufacture of each batch of drugs manufactured by him and shall retain such records, in the case of a substance for which expiry date is fixed for a period of two years from the expiry of such date and, in the case of other substances, for a period of five years from the date of manufacture. (c) The licensee shall either in his own laboratory or, where so authorised under the proviso to clause (e) of rule 16, in any other laboratory approved by the Central Licensing Board, test each batch of the raw materials used by him for the manufacture of drugs and also each batch of the final drug, shall maintain records showing the particulars in respect of such tests as specified in Schedule B-III and shall retain such records, in the case of a substance for which expiry date is fixed for a period of two years from the expiry of such date and, in the case of other substances, for a period of five years from the date of manufacture. 20A. Contract Manufacture.-- Manufacture or analysis on contract is permissible on behalf of a licensee or of a pharmaceutical company whose products are registered in Pakistan for sale subject to the conditions laid down in Schedule G," as a special case and for genuine reasons as approved by the Registration Board. SCHEDULE ‘G’ 1.2 General.-- Contract production and analysis shall be correctly defined, agreed and controlled in order to avoid misunderstandings that could result in a drug or work or analysis of unsatisfactory quality. A written contract between the contract giver and the contract acceptor shall clearly establish the duties of each party had state the way in which the authorized person shall exercise his full responsibility in releasing each batch of product for sale or issuing the certificate of analysis and a copy of such a contract shall be supplied to the Central Licensing Board also. 1.3 All arrangements for contract manufacture and analysis, including any proposed changes in technical or other arrangements, shall be in accordance with the registration of the drug concerned. 1.4 There shall be a written contract covering the manufacture and or analysis arranged, under contract and any technical arrangements made in connection with it. 1.5 The contract shall permit the contract giver to audit the facilities of the contract acceptor. 1.6 In the case of contract analysis, the final approval for release must be given by the authorised person(s). 2. Contract Giver 2.2 The contract giver shall provide the contract acceptor with all the information necessary to carry out the contracted operations correctly in accordance with the registration and any other legal requirements and the contract giver shall ensure that the contract acceptor is fully aware of any problem associated with the product, work, or tests that might pose a hazard to premises, equipment , personnel, other materials or other products. 2.3 The contract giver shall ensure that all processed products and materials delivered by the contract acceptor to comply with their specifications or that the product has been released by the authorised person(s). 3. Contract acceptor 3.2 The contract acceptor shall refrain from any activity that may adversely affect the quality of the product manufactured and or analyzed for the contract giver. 4. The contract 4.2 The contract shall specify the way in which the authorized person releasing the batch for sale ensures that each batch has been manufactured in, and checked for, compliance with the requirements of the marketing authorization. 4.3 The contract shall be describe clearly who is responsible for purchasing, testing and releasing materials and for undertaking production and quality controls, including in-process controls, and who has responsibility for sampling and analysis, and in the case of contract analysis, the contract shall state whether or not the contract acceptor shall take samples at the premises of the manufacturer. 4.4 Manufacturing, analytical and distribution records and reference samples shall be kept by, or be available to, the contract giver, and any records relevant to assessing the quality of a product in the event of complaints or a suspected defect shall be accessible and specified in the defect or recall procedures of the contract giver. 4.5 The contract shall describe the handling of starting materials, intermediate and bulk products and finished products if they are rejected and it shall also describe the processing of information if the contract analysis shows that the tested product must be rejected. 21. Licence to manufacture drugs for experimental purposes: (1) If a person intending to manufacture a drug for experimental purposes does not hold a licence to manufacture drugs, he shall before commencing such manufacture, apply in Form 3 for the grant or renewal of a licence to the Central Licensing Board addressed to its Secretary. (2) An application under sub-rule (1) shall be countersigned by the head of the institution in which,. or the director or manager of the firm or company by which, the drug will be manufactured. (3) The licence for the manufacture of drugs for experimental purposes shall be in Form 4. 22. Conditions of licence to manufacture drugs for experimental proposes: A licence issuing under rule 21 shall be subject to the following conditions, namely :-- (a) That licensee shall use the drugs manufactured under the licence exclusively for experimental purposes and shall carry on the manufacture and experimental work at the place specified in the licence. (b) The licensee shall allow a member of the Central Licensing Board or of a Provincial Quality Control Board or an Inspector to enter, with or without notice, the premises where the drugs are manufactured and to satisfy himself that the manufacture is being conducted for experimental purposes. (C) The licensee shall comply with such further requirements, if any, as may be specified under any rule subsequently made. 23. Labeling of drugs manufactured for experimental purposes: (l) Any d-rug manufactured for experimental purposes shall be kept in containers bearing labels indicating the purpose for which it has been manufactured. (2) If any drug manufactured for experimental purposes is supplied
by the manufacturer to any other person, the container shall bear
a label on which shall be stated the name and address of the manufacturer,
the accepted scientific name of the drug, if known, or, if not known,
a reference which will enable the drug to be identified and the
purpose for which it has been manufactured. (2) The Registration Board may refer any case for detailed .examination to the committee of experts on the Drugs Evaluation constituted under Section 10 of the Act. (3) The Registration Board may appoint a sub-committee consisting of at least one Clinical Professor, one pharmacologist and one pharmacist to make a detailed examination of each case and to submit a report for the consideration of the Board. (4) The Registration Board may appoint a panel of experts or inspectors to inspect on behalf of the Board the premises of a manufacturer of drugs and to submit its report to the Board. (5) The Chairman and the Secretary of the Registration Board shall, after the Board has approved the registration of a drug, sign the certificate of registration. (6) For the manner and conduct of the meetings of the Registration Board, the provisions of sub-rules (3), (4), (5), (6), (7), (8), and (9) of rule 8 shall mutatis mutandis apply. 25. Powers of Registration Board: The members of the Registration Board shall exercise all the powers of Inspector without restriction as the area, and shall have the powers of a Provincial Inspector in relation to Section 30. 26. Application for registration of drugs and fees thereof: (1) An application for registration of a drug shall be made in Form 5 or 5-A in duplicate to the Registration Board addressed to its Secretary, and separate application shall be made for each drug. (2) The applicant shall furnish such further information and material
as may be required by the Registration Board for the proper evaluation
of the drug. Provided that the application for the renewal of registration is made before the expiry of the validity of the certificate of registration. (3-A) Application for renewal of registration of a drug shall be
made in Form 5-B. 27. Duration of certificate of registration: A certificate of registration under this chapter, shall, unless earlier suspended or cancelled, be. in force for a period of five years from the date of Registration of the drug and may thereafter be renewed for periods not exceeding 5 years at a time. Provided that an application for the renewal of registration shall not be entertained unless it has been made within sixty days after the expiry of the registration and when an application has been made as aforesaid the registration shall subject to the orders passed on the application for the renewal continue in force for the next period of five years : Provided further that, if in the opinion of the Registration Board it is necessary so to do in the Public interest, it may provisionally register a [....] drug for period of two years. 28. Certificate of registration: A certificate of registration of drug shall be issued in Form 6. 29. Procedure for registration: (1) The Registration Board may, if it considers necessary, cause the application for registration and the information and material supplied to it under rule 26 to be evaluated by a Committee on Drugs Evaluation consisting of experts related to the aspect of the drug to be evaluated and obtain its report. (2) The Registration (2) The Registration Board may, before issuing a registration], cause the premises in which the manufacture is proposed to be conducted to be inspected by itself or by its sub-committee or by a panel of Inspectors or experts appointed by it for the purpose, which may examine all portions of the premises and the plant and appliances, inspect the process of manufacture intended to be employed and the means to be employed for standardising, if necessary, and testing the substances to be manufactured and enquire into the professional qualifications of the technical staff employed. (3) Where inspection under sub-rule (2) is carried out by a Sub-Committee or panel of experts or Inspectors appointed under the said sub-rule, it shall forward to the Registration Board a detailed report of ;he result of the inspection. (4) If the Registration Board, after such further enquiry, if any, as it may consider necessary, is satisfied of its safety, efficacy, quality and economical value or where the public interest so requires, it may register the drug and issue a certificate of registration in Form 6, subject to such specific conditions as it may specify.' (5) The Registration Board may, while registering a drug under sub-rule (4), approve the details as supplied by the applicant or approve them with amendments as it may deem fit in respect of the following particulars, namely :-- (a) the name under which the drug may be sold; (d) Omitted by S.R.O. 551(1)//93, dated 3. 7. 1993. (5-A) Where the Registration Board registers a new drug, it may recommend to the Federal Government for fixation of maximum price of such drug. (6) The Registration Board shall, before registering a new drug for which the research work has been conducted in other countries and its efficacy, safety and quality has been established therein, require the investigation on such pharmaceutical, pharmacological and other aspects, to be conducted and clinical trials to be made as are necessary to establish its quality and, where applicable, the biological, availability, and its safety and efficacy to be established under the local conditions: Provided that under special circumstances to be recorded in writing, the Registration Board may register a drug and require such investigations and clinical trials to be conducted after its registration. (7) A new drug, where new method of manufacture is contemplated or a change is proposed in source, standard or specification of the active ingredient or the finished product, may not require full investigations and clinical trials except in so far as they are necessary for the purpose of establishing bio-equivalence, absorption, acceptability or other such features. (8) Where it is necessary in the public interest so to do, the Registration Board may register a drug on its own motion without having received any application for registration. (9) If the Registration Board is not satisfied as to the safety, efficacy, quality or economic value of a drug, or where the public interest so requires it may, [ .]..., reject the application for registration and inform the applicant of the reasons for such rejection in writing. (10) Rejection of an application for the registration of a drug shall not debar an applicant from submitting a fresh application under rule 26. 30. Conditions or registration of drug: (1) The relevant provisions of the Ordinance and the rules in respect of the registered drug, shall be complied with. (2) The import, manufacture and sale of drugs shall be in accordance with the information contained in the applications in respect of those drugs or in any supplementary information or, where such information was amended by the Registration Board, in accordance with such amended information on the basis of which such drugs were registered: Provided that deviations from any such information may be made only after obtaining prior approval of the Registration Board. (3) The indications, contra-indication, side effects, the dosage and cautions, if any, as have been approved for the purpose of registration of a drug shall be clearly specified in the labelling and promotion. (4) Every drug shall be produced in sufficient quantity so as to ensure its regular and adequate supply in the market. (5) The manufacture of any drug shall not, without the prior approval of the Registration Board, be discontinued for period which may result in its shortage: Provided that in the circumstances beyond the control of a manufacturer,, of a drug which may lead to reduction in the production of that drug, the circumstances may be intimated to the Registration Board. (6) A record of quarterly production and disposal of a drug shall be maintained and supplied to the Chairman of the Registration Board in Form 7 in the months of January, April, July and October each year. (7) In case of an imported drug, the indenter or any other approved representative in Pakistan of the foreign firm shall ensure regular and adequate supply of tee drug in Pakistan. (7-A) The indenter, importer or manufacturer's authorised agent shall issue a warranty in Form 2-A for any drug indented or sold by him for the purpose of re-sale or distribution; and (8) In respect of new drug, records, including adequately organised and indexed files, shall be maintained containing full information regarding-- (a) animal or clinical investigations and tests conducted by the
manufacturer or reported to him by any person concerning (9) The following information shall be supplied to the Registration
Board-- (10) If a drug or any of its ingredients, which is imported or manufactured by a company in Pakistan is also approved for registration and free sale by its subsidiary, sister concern, associate or parent company in the country where it was originally developed or in any of the countries namely, USA, European Union Countries, Canada, Japan, Australia, and-- (a) if that drug at any time, for safety reasons is withdrawn or banned or certain restrictions are imposed in any of the said countries, then it shall be the responsibility of the manufacturer in Pakistan or as the case may be, the indentor, to immediately withdraw the drug from the market in Pakistan or, as the case may be to impose similar restriction and to inform the registration Board within fourteen days of such an information having come to his knowledge and having taken the necessary action. The Registration Board after getting the said intimation shall take similar action for the same drug available from other sources within the shortest possible time; (b) if a clinical information for a drug is approved by the Drug Regulatory Authority in any of the said countries, the same clinical information shall be considered as approved for drug registration in Pakistan unless modified by the Registration Board on the basis of scientific data available to it, and such clinical information may include indication, contra-indications, side effects, precautions, dosage, etc; (c) if any adverse drug reaction not otherwise included in the application for registration, is registration, is registered in any of the said countries, it shall be the responsibility of the concerned manufacturer or in case of imported drugs the indentor or manufacturer's agent in Pakistan, to be aware of such adverse action and to report to the Registration Board within thirty days of becoming so aware. (11) The manufacturer or as the case may be, the indentor shall follow the ethical criteria for medical drug promotion as given in Schedule G. (12) The manufacturer or, as the case may be, the indentor shall
supply the information in relation to safety, efficacy, production,
quality, or availability of the drugs as and when required by the
Registration Board with a view to ensure safety, efficacy or quality
of the drug, and Provided that the Federal Government may, if in its opinion the public interest so required, withdraw the approval granted to any advertisement or modify or alter any condition subject to which the advertisement was approved. (1-A) An application for advertisement of any drug, substance, remedy, treatment or offer of treatment for any disease shall be made it Form-8, addressed to the Secretary of the Commissioner on Advertising and there shall be made a separate application for each advertisement. (l-B) An application under sub-rule (l-A) shall be accompanied by the proper fee specified in Schedule F : and (1-C) The approval of the advertisement, granted under sub-rule (1), shall be valid for a period of two years only. (2) A drug or any substance referred to in clause (ii) of Sec. 24 may be advertised to the medical, pharmaceutical and allied professions, without referring to the Federal Government, through medical representatives or through professional journals and publication which are meant for circulation exclusively amongst the members of the medical, pharmaceutical and allied professions • Provided that: (3) Advertisements under sub-rule (2) shall be subjected to the
following conditions, namely :-- (4) A drug or any substance referred to in clause (ii) of Section 24, may be advertised through Press without reference to the Federal Government if it is merely intended to inform the public of the availability or the price of such drug or any substance referred to in clause (ii) of Section 24 subject to the condition that the Federal Government may prohibit such advertisement if, in its opinion, the public interest so requires. (5) A drug or any substance referred to in clause (ii) of Section 24, may be advertised to the medical, pharmaceutical and allied professions through a documentary film. (6) No advertisement under this rule shall contain any direct or indirect comparison in any way with any other drug or substance or remedy for any disease for the purpose of attracting customers or with a view to discredit other such product. (7) Advertisement material shall be presented with courtesy and good taste and words and phrases implying urgency, uniqueness or such expressions which are absolute in character, such as "the most potent", "the most rapid", "the most efficacious", or which make exaggerated claims or to general claims, such as "effective in all cases" or "effective against all complaints" or superlatives shall be avoided. (8) Advertisement of a drug or any substance referred to in clause (ii) of Section 24 shall include such information or any risks and other precautions as may be necessary for the protection of public health, and in the case of drug also its maximum retail price fixed under Section 12. (9) No drug or any other substance shall be advertised in a manner which encourages self-medication or use to the extent that it endangers health. (10) No drug or any remedy, treatment or after treatment of any disease specified in Schedule 'E' shall be advertised except as provided in sub-rule (2). (11) Reminder publications for the medical, pharmaceutical and allied professions shall include the name of the drug and its exact composition, the price, the name and address of the manufacturer and a statement to the effect that "Full information is available on request". 32. Sampling of drugs: Samples of drugs may be provided to the physicians or dentists or Pharmacists or Veterinarians or a medical institution in a reasonable quantity and in reduced packings marked with the words "Physicians Sample Not for Sale". 33. Expenditure on advertisement: No person shall spend more than five per cent of his turnover on advertisement, sampling and other promotional activities in respect of drugs, Explanation: The expenditure on pay and allowances of the field force connected with the promotional activities shall not be included in expenditure for the purpose of this rule. 34. Substances required to be prescribed under Section 24: Any substance or a mixture of substances offered for sale which is injurious, or likely to become hazardous, to the health of a person shall be deemed to be a substance for the purpose of Section 24 of the Ordinance. 35. Retailer's discount: The retailers discount shall be 15% of
the maximum retail price. 2. The drug(s) or class(es) of drugs intended to be manufactured
:- 3. I enclose :- (i) Particulars regarding the legal status of the applicant (i.e. in case of proprietorship the names) of proprietors and their address (es), in the case of firm the name and names and addresses of its partners and in the case of company the name and address of the company and its directors). (ii) Details of the premises including layout plan of the factory. (iii) Details of the section-wise equipment and machinery for manufacture and quality control. (iv) Names and qualifications of the Production Incharge and Quality Control Incharge for supervising manufacturing processes and Quality Control Department, and other technical staff working in these departments. 4. The premises and plan will be ready for inspectionon or are
ready for inspection. Note: Copies of balance sheets to be enclosed with the application for renewal only"; and (6) in. Schedule B, in paragraph (2), in clause (k), for the semi colon and word"; and" a colon shall be substituted and thereafter the following proviso shall be inserted, namely: Provided that the conditions of location may be relaxed by the
Board in suitable cases for grant or renewal or a licence subject
to such conditions as it may deem fit, if the surroundings and the
premises, in the opinion of the Board, are satisfactory for the
intended manufacture. 2. The drug(s) or class(es)of drugs intended to be continued to
be manufactured:- 3. There have been/have not been any change in respect of 4. Statement of the Central Research Fund. Attested copies of the last two income tax assessment orders of
the Income Tax Department attached. 2. This licence permits the manufacture of 3. This licence shall, in addition to the conditions specified in the rules made under the Drugs Ordinance/Act, 1976, be subject to the following conditions namely:- (i) The licence will be in force for a period of five years from the date of issue unless earlier suspended or cancelled. (ii) The licence authorises the sale by way of wholesale dealing and storage for sale by the licensee of the products manufactured under this licence, subject to the conditions applicable to licences for sale. (iii) Name of the approved expert staff. FORM 2A 2. Description of bill of sale, invoice, bill of lading or other
document (if any). 1. Name and quantity of drug(s) to be manufactured for the said
purposes:. FORM 4 2. The licence is subject to the conditions prescribed in rule 22 of the Drugs (Licensing, Registering and Advertising) Rules, 1976, and such other conditions as n3ay be subsequently prescribed or Specified by the Central Licensing Board in this behalf. 3. This licence shall unless previously suspended or cancelled be in force for a period of two years from the date specified below:- Name of drugs with quantity to be manufactured. FORM 5 2, Name of drug • 3 Name under which drug is proposed to be sold 4. Dosage from of the drug: 5. Composition of the drug, stating quantity of each active and non-active ingredient(s) per unit or as a percent age of total formulation : 6. Proposed dosage : 7. Main Pharmacological group to which the drug belongs: 8. Pharmacological and clinical data : 9. Proposed route of administration. 10. Description of the method of manufacture and quality control with details of the equipment. 11. Specifications, with details of analytical procedure for each ingredient and the finished drugs (not required in case of a drug for which pharmacopocial standards recognised under the Drugs Act, 1976, are claimed). 12. Bio-availability, Bio-equivalence and Pharmacokinetics Analysis (For Dosage Form Introducing first time in Pakistan). 13. Stability Summary : (b) Shelf-life when stored under expected or directed storage conditions. (c) Recommended storage conditions and expiration date to be assigned to the specific formulation and package.. (d) Extreme Temperature Fluctuations Study for all liquid and semi-solid preparations. (Such observations should be utilized for appropriate labelled storage conditions or warning statements). (e) Type of container/package, with the nature of material, package testing (chemical, mechanical, environmental). 14. Labelling : Specimen or draft with colour scheme, alongwith the undertaking to refrain from counterfeiting shall also be submitted. 15. Pack size (s) and proposed maximum retail price with the following
details:- 16. Justification : (Only in case of a new entity). 17. Patent number, if any, with date and its date of expiry. 18. In case of a new drug (entity) not yet registered in Pakistan
: (ii) Any other relevant information that may be required by the
Board for consideration of this application. 4. Name of drug, under which it is proposed to be sod: 8. Main Pharmacological group to which the drug belongs: 9. Proposed route of administration: 10. Pharmacological and clinical data : 11. Specifications with details of analytical procedure (not required in case of a drug for which the pharmacopocial standards recognised under the Drugs Act, 1976 are claimed): 12. Bio-availability studies: 13. Stability studies : 14. Proposed shelf life with storage conditions, if any : 15 Type of container : 16. Labelling : (Specimen to be enclosed alongwith a .sample and undertaking to refrain from counterfeiting shall also be submitted) : 17. Proposed C and F and maximum retail price (in case of imported drug) : 18. Justification : 19. Certificate regarding sale and G.M.P. in the country of origin (in English and in Form 5 (c) : 20. Certificate of registration by F.D.A. of USA. Committee on Safety of Medicines of U.K. or corresponding agencies of France, West Germany, Japan, Sweden. and Denmark. 21. Patent number, if any, with date and its date of expiry : 22. Undertaking to manufacture drug locally within two years. If
it is not possible, the reasons therefor. 1. Name and address of the manufacturer: Manufacturer and or when applicable the person responsible for Placing the Product on the market ............................ Address(es)...................................................................... It is certified : It is also certified that (a) the manufacturing plant in which
the product is produced is subject in inspections at suitable intervals,
and (b) the manufacturer conforms to requirements for good practices
in the manufacture and quality control, in respect of products to
be sold or distributed within the country of origin or to be exported. 2. This registration shall be valid for a period of five years unless earlier suspended or cancelled. 3. This registration is subject to the conditions specified in
the Drugs Ordinance/Act, 1976, and .the rules thereunder and to
the conditions specified in the enclosure.
SCHEDULE B CONDITIONS FOR GRANT OF A LICENSE TO MANUFACTURE BY WAY OF FORMULATION SECTION-I REQUIREMENTS OF PLANT AND EQUIPMENT (B) The following equipment is required for manufacture of Syrups,
Exlixirs and Solutions :-- (C) Equipment for the manufacture of Pills and Compressed Tablets
including Hypodermic Tablets. For efficient operation, the tablet
production department shall be divided into the following three
distinct and separate sections situated in different rooms, 1. Granulating Section: (1) Disintegrator, where applicable. 2. Tableting Section: The Tableting Section shall be free from dust and floating particles. For this purpose, it is desirable that each tablet machine is connected either to an exhaust system or isolated into cubicles. 3. Coating Section: The coating section shall be made dust-free and suitable exhaust provided to remove excess powder and the fumes resulting from solvent evaporation. A total area of not less than 900 square feet for the three Sections is required for basic installations. The manufacture of Hypodermic Tablets shall be conducted under aseptic conditions in a separate air-conditioned room, the walls of which shall be smooth and washable. The granulation, tableting and packing shall be done in this room. (D) The following equipment is required for the manufacture of
Powders :-- In the case of operations involving floating particles of fine powder or dust a suitable exhaust system shall be provided, Workers shall be provided with suitable marks during operation. If a manufacturer has e tablet section where the powder of the granules can be manufactured, provided that such granules or powder or non toxic, no separate equipment will be required for manufacture of such powder as granules. (E) The following equipment is required for filling of Hard Gelatin Capsules:- (1) Mixing and blending equipment. (2) Capsule filling units. (F) The following equipment is required for ,the manufacture of
Surgical Dressings other than Absorbent Cotton Wool An area of minimum of 300 square feet is required for the basic installations. In case medicated dressings are to be manufactured, room with an area of minimum of 300 square feet shall be provided. (G) The following equipment is required for the manufacture under aseptic conditions of Eye-Ointments, Eye-Drops, Eye-Lotions and other use :- (1) Hot air oven electrically heated with thermostatic control. | |