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Subpart A-Specific Sector Provi

sions for Pharmaceutical Good Manufacturing Practices

(d) Inspection means an onsite evaluation of a manufacturing facility to determine whether such manufacturing facility is operating in compliance with GMP's and/or commitments made as part of the approval to market a product.

(e) Inspection report means the written observations and GMP's compliance assessment completed by an authority listed in Appendix B of this subpart.

(f) Regulatory system means the body of legal requirements for GMP's, inspections, and enforcements that ensure public health protection and legal authority to assure adherence to these requirements. [63 FR 60141, Nov. 6, 1998; 64 FR 16348, Apr. 5, 1999]

$26.1 Definitions.

(a) Enforcement means action taken by an authority to protect the public from products of suspect quality, safety, and effectiveness or to assure that products are manufactured in compliance with appropriate laws, regulations, standards, and commitments made as part of the approval to market a product.

(b) Equivalence of the regulatory systems means that the systems are sufficiently comparable to assure that the process of inspection and the ensuing inspection reports will provide adequate information to determine whether respective statutory and regulatory requirements of the authorities have been fulfilled. Equivalence does not require that the respective regulatory systems have identical procedures.

(c) Good Manufacturing Practices (GMP's). [The United States has clarified its interpretation that under the MRA, paragraph (c)(1) of this section has to be understood as the U.S. definition and paragraph (c)(2) as the EC definition.]

(1) GMP's mean the requirements found in the legislations, regulations, and administrative provisions for methods to be used in, and the facilities or controls to be used for, the manufacturing, processing, packing, and/or holding of a drug to assure that such drug meets the requirements as to safety, and has the identity and strength, and meets the quality and purity characteristics that it purports or is represented to possess.

(2) GMP's are that part of quality assurance which ensures that products are consistently produced and controlled to quality standards. For the purpose of this bpart, GMP's include, therefore, the system whereby the manufacturer receives the specifications of the product and/or process from the marketing authorization/ product authorization or license holder or applicant and ensures the product is made in compliance with its specifications (qualified person certification in the EC).

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$26.2 Purpose.

The provisions of this subpart govern the exchange between the parties and normal endorsement by the receiving regulatory authority of official good manufacturing practices (GMP's) inspection reports after a transitional period aimed at determination of the equivalence of the regulatory systems of the parties, which is the cornerstone of this subpart. 8 26.3 Scope.

(a) The provisions of this subpart shall apply to pharmaceutical inspections carried out in the United States and Member States of the European Community (EC) before products are marketed (hereafter referred to "preapproval inspections”) as well as during their marketing (hereafter referred to as "postapproval inspections”).

(b) Appendix A of this subpart names the laws, regulations, and administrative provisions governing these inspections and the good manufacturing practices (GMP's) requirements.

(C) Appendix B of this subpart lists the authorities participating in activities under this subpart.

(d) Sections 26.65, 26.66, 26.67, 26.68, 26.69, and 26.70 of subpart C of this part do not apply to this subpart. $ 26.4 Product coverage.

(a) The provisions of this subpart will apply to medicinal products for human

assessing regulatory systems and the authorities' capabilities. In conducting the equivalence assessment, the parties will ensure that efforts are made to save resources.

(d) Equivalence assessment for authorities added to Appendix B of this subpart after the effective date described in $26.80(a) will be conducted as described in this subpart, as soon as practicable.

or animal use, intermediates and starting materials (as referred to in the European Community (EC)) and to drugs for human or animal use, biological products for human use, and active pharmaceutical ingredients (as referred to in the United States), only to the extent they are regulated by the authorities of both parties as listed in Appendix B of this subpart.

(b) Human blood, human plasma, human tissues and organs, and veterinary immunologicals (under 9 CFR 101.2, “veterinary immunologicals” are referred to as “veterinary biologicals”) are excluded from the scope of this subpart. Human plasma derivatives (such as immunoglobulins and albumin), investigational medicinal products/new drugs, human radiopharmaceuticals, and medicinal gases are also excluded during the transition phase; their situation will be reconsidered at the end of the transition period. Products regulated by the Food and Drug Administration's Center for Biologics Evaluation and Research as devices are not covered under this subpart.

(c) Appendix C of this subpart contains an indicative list of products covered by this subpart.

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§ 26.5 Length of transition period.

A 3-year transition period will start immediately after the effective date described in § 26.80(a).

8 26.6 Equivalence assessment.

(a) The criteria to be used by the parties to assess equivalence are listed in Appendix D of this subpart. Information pertaining to the criteria under European Community (EC) competence will be provided by the EC.

(b) The authorities of the parties will establish and communicate to each other their draft programs for assessing the equivalence of the respective regulatory systems in terms of quality assurance of the products and consumer protection. These programs will be carried out, as deemed necessary by the regulatory authorities, for postand preapproval inspections and for various product classes or processes.

(c) The equivalence assessment shall include information exchanges (including inspection reports), joint training, and joint inspections for the purpose of

§ 26.9 Equivalence determination.

(a) Equivalence is established by having in place regulatory systems covering the criteria referred to in Appendix D of this subpart, and a demonstrated pattern of consistent performance in accordance with these criteria. A list of authorities determined as equivalent shall be agreed to by the Joint Sectoral Committee at the end of the transition period, with reference to any limitation in terms of inspection type (e.g., postapproval or preapproval) or product classes or processes.

(b) The parties will document insufficient evidence of equivalence, lack of opportunity to assess equivalence or a determination of nonequivalence, in sufficient detail to allow the authority being assessed to know how to attain equivalence. $ 26.10 Regulatory authorities not list

ed as currently equivalent. Authorities not currently listed as equivalent, or not equivalent for certain types of inspections, product

classes or processes may apply for re- alent, will be provided to the authority consideration of their status once the of the importing party. Based on the necessary corrective measures have determination of equivalence in light been taken or additional experience is of the experience gained, these inspecgained.

tion reports will normally be endorsed

by the authority of the importing § 26.11 Start of operational period.

party, except under specific and delin(a) The operational period shall start eated circumstances. Examples of such at the end of the transition period and circumstances include indications of its provisions apply to inspection re- material inconsistencies or inadequaports generated by authorities listed as cies in an inspection report, quality deequivalent for the inspections per- fects identified in the postmarket surformed in their territory.

veillance or other specific evidence of (b) In addition, when an authority is serious concern in relation to product not listed as equivalent based on ade- quality or consumer safety. In such quate experience gained during the cases, the authority of the importing transition period, the Food and Drug party may request clarification from Administration (FDA) will accept for the authority of the exporting party normal endorsement (as provided in which may lead to a request for rein$26.12) inspection reports generated as spection. The authorities will endeavor a result of inspections conducted joint- to respond to requests for clarification ly by that authority on its territory in a timely manner. and another authority listed as equiva- (b) Where divergence is not clarified lent, provided that the authority of the in this process, an authority of the imMember State in which the inspection porting country may carry out an inis performed can guarantee enforce- spection of the production facility. ment of the findings of the inspection report and require that corrective

§ 26.13 Transmission of postapproval measures be taken when necessary.

inspection reports. FDA has the option to participate in Postapproval good manufacturing these inspections, and based on experi- practice (GMP) inspection reports conence gained during the transition pe- cerning products covered by this subriod, the parties will agree on proce- part will be transmitted to the authordures for exercising this option.

ity of the importing country within 60(c) In the European Community (EC), calendar days of the request. Should a the qualified person will be relieved of new inspection be needed, the inspecresponsibility for carrying the controls tion report will be transmitted within laid down in Article 22 paragraph 1(b) 90-calendar days of the request. of Council Directive 75/319/EEC (see Appendix A of this subpart) provided that

$ 26.14 Transmission of preapproval these controls have been carried out in

inspection reports. the United States and that each batch/ (a) A preliminary notification that lot is accompanied by a batch certifi- an inspection may have to take place cate (in accordance with the World will be made as soon as possible. Health Organization Certification (b) Within 15-calendar days, the relScheme on the Quality of Medicinal evant authority will acknowledge reProducts) issued by the manufacturer ceipt of the request and confirm its certifying that the product complies ability to carry out the inspection. In with requirements of the marketing the European Community (EC), reauthorization and signed by the person quests will be sent directly to the relresponsible for releasing the batch/lot. evant authority, with a copy to the Eu

ropean Agency for the Evaluation of $ 26.12 Nature of recognition of inspec- Medicinal Products (EMEA). If the aution reports.

thority receiving the request cannot (a) Inspection reports (containing in- carry out the inspection as requested, formation as established under $26.8), the requesting authority shall have the including a good manufacturing prac- right to conduct the inspection. tice (GMP) compliance assessment, (c) Reports of preapproval inspecprepared by authorities listed as equiv- tions will be sent within 45-calendar

by the parties on the future status of that authority.

days of the request that transmitted the appropriate information and detailed the precise issues to be addressed during the inspection. A shorter time may be necessary in exceptional cases and these will be described in the request.

$ 26.15 Monitoring continued equiva

lence. Monitoring activities for the purpose of maintaining equivalence shall include review of the exchange of inspection reports and their quality and timeliness; performance of a limited number of joint inspections; and the conduct of common training sessions.

$26.16 Suspension.

(a) Each party has the right to contest the equivalence of a regulatory authority. This right will be exercised in an objective and reasoned manner in writing to the other party.

(b) The issue shall be discussed in the Joint Sectoral Committee promptly upon such notification. Where the Joint Sectoral Committee determines that verification of equivalence is required, it may be carried out jointly by the parties in a timely manner, under 8 26.6.

(c) Efforts will be made by the Joint Sectoral Committee to reach unanimous consent on the appropriate action. If agreement to suspend is reached in the Joint Sectoral Committee, an authority may be suspended immediately thereafter. If no agreement is reached in the Joint Sectoral Committee, the matter is referred to the Joint Committee as described in 8 26.73. If no unanimous consent is reached within 30 days after such notification, the contested authority will be suspended.

(d) Upon the suspension of authority previously listed as equivalent, a party is no longer obligated to normally endorse the inspection reports of the suspended authority. A party shall continue to normally endorse the inspection reports of that authority prior to suspension, unless the authority of the receiving party decides otherwise based on health or safety considerations. The suspension will remain in effect until unanimous consent has been reached

$ 26.17 Role and composition of the

Joint Sectoral Committee. (a) A Joint Sectoral Committee is set up to monitor the activities under both the transitional and operational phases of this subpart.

(b) The Joint Sectoral Committee will be cochaired by a representative of the Food and Drug Administration (FDA) for the United States and a representative of the European Community (EC) who each will have one vote. Decisions will be taken by unanimous consent.

(c) The Joint Sectoral Committee's functions will include:

(1) Making a joint assessment, which must be agreed by both parties, of the equivalence of the respective authorities;

(2) Developing and maintaining the list of equivalent authorities, including any limitation in terms of inspecting type or products, and communicating the list to all authorities and the Joint Committee;

(3) Providing a forum to discuss issues relating to this subpart, including concerns that an authority may be no longer equivalent and opportunity to review product coverage; and

(4) Consideration of the issue of suspension.

(d) The Joint Sectoral Committee shall meet at the request of either party and, unless the cochairs otherwise agree, at least once each year. The Joint Committee will be kept informed of the agenda and conclusions of meetings of the Joint Sectoral Committee.

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$26.19 Information relating to quality

aspects. The authorities will establish an appropriate means of exchanging information on any confirmed problem reports, corrective actions, recalls, rejected import consignments, and other regulatory and enforcement problems for products subject to this subpart. 8 26.20 Alert system.

(a) The details of an alert system will be developed during the transitional period. The system will be maintained in place at all times. Elements to be considered in developing such a system are described in Appendix E of this subpart.

(b) Contact points will be agreed between both parties to permit authorities to be made aware with the appropriate speed in case of quality defect, recalls, counterfeiting, and other problems concerning quality, which could necessitate additional controls or suspension of the distribution of the product.

Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation, or administrative action relating to proprietary medicinal products as extended, widened, and amended. Council Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products as extended, widened and amended. Council Directive 81/851/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to veterinary medicinal products, as widened and amended. Commission Directive 91/356/EEC of 13 June 1991 laying down the principles and guidelines of good manufacturing practice for medicinal products for human use. Commission Directive 91/412/EEC of 23 July 1991 laying down the principles and guidelines of good manufacturing practice for veterinary medicinal products. Council Regulation EEC No 2309/93 of 22 July 1993 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products. Council Directive 92/25/EEC of 31 March 1992 on the wholesale distribution of medicinal products for human use. Guide to Good Distribution Practice (94/C 63/ 03). Current version of the Guide to Good Manufacturing Practice, Rules Governing Medicinal Products in the European Community, Volume IV.

$ 26.21 Safeguard clause.

Each party recognizes that the importing country has a right to fulfill its legal responsibilities by taking actions necessary to ensure the protection of human and animal health at the level of protection it deems appropriate. This includes the suspension of the distribution, product detention at the border of the importing country, withdrawal of the batches and any request for additional information or inspection as provided in $26.12.

2. For the United States:

APPENDIX A TO SUBPART A OF PART 26%

LIST OF APPLICABLE LAWS, REGULA-
TIONS, AND ADMINISTRATIVE PROVI-
SIONS

[Copies of FDA documents may be obtained from the Government Printing Office, 1510 H St. NW., Washington, DC 20005. FDA documents, except the FDA Compliance Program Guidance Manual, may be viewed on FDA's Internet web site at "http://www.FDA.gov”.] Relevant sections of the United States Federal Food, Drug, and Cosmetic Act and the United States Public Health Service Act. Relevant sections of Title 21, United States Code of Federal Regulations (CFR) Parts 199, Parts 200-299, Parts 500-599, and Parts 600 799. Relevant sections of the FDA Investigations Operations Manual, the FDA Regulatory Procedures Manual, the FDA Compliance Policy Guidance Manual, the FDA Compliance Program Guidance Manual, and other FDA guidances.

1. For the European Community (EC): [Copies of EC documents may be obtained from the European Document Research, 1100 17th St. NW., suite 301, Washington, DC 20036. EC documents may be viewed on the European Commission Pharmaceuticals Units web site at “http://dg3.eudra.org”.]

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