---Submitted Electronically---

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1 ` Pfizer Inc 100 Route 206 North Peapack, NJ August 8, Submitted Electronically--- Food & Drug Administration 5600 Fishers Lane Rockville, MD Subject: Docket Nos. FDA 2013 N 0683, FDA 2013 N 0684, and FDA 2013 N 0685 Food and Drug Administration Safety and Innovation Act Title VII Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of Commercial Importers and Good Importer Practices Dear Madam/Sir: Pfizer appreciates the opportunity to submit comments in response to the important questions raised in Sections of the Food Drug Administration Safety and Innovation Act (FDASIA). Pfizer strongly supports the mission of the FDA to ensure patients receive the highest quality medicines, as well as its role protecting them from unsafe imported drugs. Pfizer's mission is to be the premier, innovative biopharmaceutical company. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for our patients. We believe firms have a responsibility to protect the integrity of their supply chains. Pfizer applauds FDA s efforts to promulgate effective supply chain regulations pursuant to FDASIA and looks forward to partnering in the development of associated guidance and regulations. Pfizer would like to set forth, as general principles that: 1) we encourage the Agency, in promulgating the regulations required by Sec. 713, to incorporate the concept allowed under Section 801(r)(4)(B)(i), establishing that importers and types of imports may be differentiated on the basis of risk; 2) importers willing to demonstrate strong internal controls to protect the supply chain from incursion should be may proceeded, at the time of entry, upon submission of minimal incremental information; 3) FDA should coordinate with Customs & Border Protection (CBP) to implement a process enabling one channel of data to accomplish all steps necessary to complete the import process for both agencies; 4) trusted importers should receive the benefit of account management whereby transactional review, when necessary, is conducted by a centralized dedicated team comprised of FDA and CBP officials familiar with the importer and its business operations. Pfizer has provided below responses to questions raised in the Federal Register notice. We acknowledge that many of these matters require more extensive discussion and study. Thus, we believe thoughtful dialog with stakeholders from government, trade, and other stakeholders within a Federal Advisory Committee (FAC), in collaboration with the Customs & Border Protection Advisory Committee on Commercial Operations of Customs and Border Protection (COAC), would yield the best solutions for effective border management of evolving risks, such as those arising from illicit traffic in short supply drugs and excipients. Pfizer would be pleased to participate in such a panel. If establishment of a FAC is not possible, within the rule making time frame, we suggest FDA set up workshop-style meetings before the publication of proposed rule, or during the comment period of the proposed rule, to facilitate such a dialog.

2 Page 2 A. Section 713: Standards for Admission of Imported Drugs 1. How should the regulations implementing section 801(r) of the FD&C Act (21 U.S.C. 381(r)), as amended by section 713 of FDASIA, define importer as that term is used in 801(r)(l)? Pfizer recommends that the regulations define importer as defined in Title VII of the Food, Drug & Cosmetic Act, Section 805, referencing supplier verification wherein importer" is defined as A) the United States owner or consignee, other than logistics service providers, [of the article of food] at the time of entry of such article into the United States; or (B) in the case when there is no United States owner or consignee as described in subparagraph (A), the United States agent or representative of a foreign owner [or consignee of the article of food] at the time of entry of such article into the United States. 2. What information should FDA require importers to submit at the time of entry that would demonstrate a drug s compliance with applicable requirements of the FD&C Act as a condition of granting admission of the drug into the United States? Pfizer believes that importers should be categorized according to risk: a) trusted importers; b) low risk; and c) unknown risk. Trusted Importers should be those that demonstrate internal controls that exceed minimal quality and supply chain integrity standards, and apply for and are approved by the FDA to participate as a certified- trusted importer. We believe that trusted importers should only be required to file, at the time of entry, a certified-trusted importer affirmation of compliance code (AOC) conveying they have been approved for entry without further documentation. In addition, the following minimal data should be required for risk targeting. o Unique manufacturing facility identifier o CBP advanced security data Low risk importers are those with an acceptable history of compliance that have not applied for certified importer status. For this category, the following data should be provided and validated by FDA. o Appropriate application number (NDA, ANDA, IND) o Unique manufacturing facility identifier o Product description o Drug listing number o FDA product code o Quantity o Additional AOC codes defining the import scenario (eg samples, non-human use) o CBP entry data The Unknown category of importer represents the highest risk. It represents that population of importers with a negative or no compliance history. This category should trigger both document and physical exams with particular emphasis on the ability to demonstrate the inbound logistics of the consignment. Low risk importers should be required to file, at the time of entry, data now required for Predictive Risk Risk-based Evaluation for Dynamic Import Compliance Targeting (PREDICT) processing.

3 Page 3 Unknown importers should also be required to file PREDICT data, in addition to other proofs of product integrity, such as: recent current good manufacturing processes (cgmp) or facility inspection certificates covering the production date of the imported lot; bills of lading evidencing the place and port of loading and shipper to the United States as well as conveyance security proofs demonstrating the product has not been tampered with during transport. 3. What information could an importer submit to FDA at the time of entry to demonstrate compliance with applicable requirements of the FD&C Act relating to: a) homeopathic drugs intended for human use, No comment b. articles intended for human drug compounding, No comment c. articles intended for animal drug compounding, and No comment d. drugs intended for research? Pfizer recommends that imports of materials intended for research conducted under an investigational new drug application (IND) should be exempt from FDA border processes through an Affirmation of Compliance Code for Research (ACCR) established for the purpose. INDs include manufacturing and control information describing the composition, manufacture, and control of the drug substance and the drug product. In each phase of the investigation information is required to be submitted to assure the proper identification, quality, purity, and strength of the investigational drug. These controls are available as a function of the development processes and are dynamically sufficient to satisfy FDA s cgmp concerns such that further evidence at time of time of import would be redundant. In addition, human pharmaceutical drugs imported for non-human use (i.e., CFR ) should also be exempt from FDA border processes through an ACCR. 4. What facility information should FDA request from importers at the time of entry to help assess whether a drug complies with applicable requirements of the FD&C Act? See our response to question #2. Beyond the AOC code, a unique manufacturing facility identifier would be appropriate for all categories of importer. 5. What information could importers submit at the time of entry to demonstrate compliance with country of export regulations in accordance with section 801(r)(2)(C) of the FD&C Act? Section 801(r)(2)(C) provides that the information to be submitted as a condition of granting admission into the U.S., may include information relating to compliance with country of export regulations. Where the United States has entered into a mutual recognition agreement with another country, information relating to the US approved status of the product and thereby the manufacturing site within the other country would be

4 part of the drug filing and be known in advance of arrival into the United States. Further information at the time of entry would be redundant. Page 4 6. What information could importers submit at the time of entry to demonstrate that a drug offered for import complies with U.S. CGMP requirements? Pfizer believes that time of entry is the least efficient time to seek information demonstrating manufacturing compliance or supply chain security. Our proposal for the establishment of a certified-trusted importer program will establish the importer s compliance and product integrity before consignments ever reach the United States border. Importers that have not been admitted to a certification program should be required to present the evidence noted under Question #2. 7. What information could importers submit at the time of entry that would serve as evidence of satisfactory inspection, such as by a foreign government or an agency of a foreign government? We do not believe evidence of satisfactory inspection should be required at the time of entry. We also support FDA s efforts at improving information collection and leveraging of international regulatory counterparts. 8. Should FDA require that importers submit certificates of analysis (COAs) to the Agency as a condition of admission under section 801(r) of the FD&C Act? Requiring any documentation for admissibility determination contradicts the PREDICT system effort and the basic premises we have recommended. If so, how could an importer demonstrate a COA s authenticity? We do not believe COA s at the time of import should be used for importation purposes. 9. Section 801(r)(4)(B)(i) of the FD&C Act permits FDA, as appropriate, to consider differences among imports and types of drugs and based on the level of risk posed by the imported drug, provide for expedited clearance for those importers that volunteer to participate in partnership programs for highly compliant companies and pass a review of internal controls, including sourcing of foreign manufacturing inputs, and plant inspections. a. What criteria should FDA use to evaluate potential participants in voluntary partnership programs for highly compliant companies? There are two aspects that should be considered in evaluating companies for participation in trusted importer programs: 1) the company s compliance history and ability to manufacture quality, safe, and effective medicines, and 2) the company s history of delivering products safely through secure supply chains. In general, with regard to product safety and quality, we believe that demonstration of cgmp s and compliance history over time is the appropriate basis for assuring compliance with product quality regulations. Adherence to good distribution practices (GDP s) to assure the quality of product is maintained during transport and security standards to assure the integrity of the supply chain should also be considered in evaluating applicants for certified-trusted trader status. In that respect, we believe that participation in the Customs & Border Protection (CBP) and Transportation Security Administration (TSA) supply chain security programs are relevant and important factors in differentiating traders on a risk basis. Specifically, good standing in the CBP s Customs & Trade Partnership Against Terrorism (CTPAT) at or

5 Page 5 above Tier II, and participation in TSA s Certified Cargo Screening Program (CCSP), and programs such as Canada s Partners In Protection (PIP) are reliable demonstrations of the trader s investment in the integrity of its physical supply chain. Having a supply chain security program that strategically and holistically looks at prevention, detection, and response to supply chain security threats such as product diversion, cargo theft, intentional adulteration, and counterfeit goods demonstrates further commitment to ensuring supply chain integrity. Thus, we believe it would be appropriate to review the applicant s broad trade compliance commitment as well, by considering, for example, participation in CBP s Importer Self Assessment program, which is a voluntary federal program that results in an exemption from compliance audits based on the firm s internal controls. Companies willing to discuss and explain these internal control programs should be recognized as posing the least risk and be admitted to the voluntary trusted importer program. Demonstrated investment in product safety and integrity should avail the trusted importer the benefit of green lane passage through FDA and CBP border processes. b. How could FDA take into account differences among importers and types of drugs to allow for expedited entry as part of a voluntary partnership program? We believe a review of internal manufacturing, quality and supply integrity programs would reflect the level of risk the importer represents. Internal importer practices and procedures should demonstrate attention to the level and type of risk between importers and the types of drugs they import. This can only be ascertained by the kind of review of internal operations recommended above in 9(a). Importers not able to pass the predetermined criteria should be considered higher risk importers. In relation to product category risks, we believe details such as dosage form (e.g., parenteral vs. topical), end use of material (e.g., human vs. non-human use), product safety profile, drug shortage status, and orphan drug status are key primary criteria for consideration. Secondary criteria could include details such as perishability and whether it is a life-saving drug. c. What risk factors should FDA consider when determining drug admissibility under a voluntary partnership program? We have enumerated criteria to be considered under Question 9(a). 10. What benefits and burdens may be created by requiring drug importers to electronically submit information demonstrating that a drug complies with applicable requirements of the FD&C Act as a condition of admission? How could we minimize any possible burdens? How do we strike a reasonable balance between rigor and efficiency in requiring information that is both reliable and yet can be submitted and reviewed efficiently? As indicated in response to previous questions, we believe admissibility decisions should be made, on the basis of application to a certified-trusted importer program, before shipments ever reach the United States. In those cases in which a trusted importer AOC has not been obtained, the ability of importers to provide appropriate information to key government agencies electronically, at or prior to entry, would be of benefit to facilitate verification of the admissibility of the material. The data listed in response to question 2 above should provide enough information to support a release decision. When FDA Entry Reviewers do not have visibility of current approved NDA information, including changes that were previously filed in an Annual Report or Supplement, especially related to changes in the names of legal entities, however, delays occur, placing an undue burden on both importers and the FDA. A focused effort resulting in improved visibility to, and sharing of current registration details

6 Page 6 would help to alleviate much of this burden and provide a more efficient entry review process. Furthermore, manual FDA review of supportive, hard copy import data could be reduced by the establishment of additional Affirmation of Compliance codes that would standardize, and allow the electronic submission of supplemental import data, including non-human use samples imported for laboratory testing purposes, PLAIR, US Goods Returned and chemical intermediates exempt from drug listing/regulatory filing requirements. Another beneficial change would be the establishment of a centralized FDA review team responsible for pharmaceutical imports (similar to the Customs Center of Excellence). This would not only provide efficiencies resulting from specialized experts serving as reviewers, but also drive consistent regulation enforcement and eliminate the port-specific review practices currently in place. Additional alignment between FDA and Customs practices, specifically surrounding use of temporary import bonds for import for export (IFE) materials (e.g. material imported solely for packaging/labeling operations) would also be helpful, as well as a standardized process across ports associated with refused entry materials. B. Section 714: Registration of Commercial Importers of Drugs 1. How should the regulations implementing section 714 of FDASIA (section 801(s) of the FD&C Act) define commercial importer to ensure that the appropriate entities are required to register with FDA and meet requirements regarding good importer practices (GIP)? Should these commercial importers be the same entities as the importers required to comply with the standards for admission to be adopted under section 801(r) of the FD&C Act? The commercial importer should be subject to the same standards for admission as the manufacturer importer - required to comply with the import standards of the FD&C Act. One company importing the materials of another for the sole purpose of sale or distribution should be held to the same requirements as a company importing its own approved product for further manufacturing or distribution.. 2. Under section 801(s)(1) of the FD&C Act, the registration regulations will apply to commercial importers of drugs. A drug is defined in section 201(g)(1) of the FD&C Act (21 U.S.C. 321(g)(1)) and includes, but is not limited to, finished dosage form drug products, drugs for further processing, active pharmaceutical ingredients, and other drug components, including inactive ingredients. Should commercial importers of certain types of drugs, such as inactive ingredients, be exempt from the commercial importer registration requirements? Should the importation of drugs for certain purposes (e.g., research use) be exempt from registration? We believe finished dosage form, drugs for further processing, and active pharmaceutical ingredients should require registration. Inactive ingredients, which are not subject to new drug applications (NDAs) as individual compounds, should not require registration. There are thousands of such ingredients, many of which have multiple uses including non pharmaceutical manufacturing,. In considering the applicant for certified importer status, however, internal controls covering inactive ingredients should be considered. Where the importer is also the excipient-user, the entity is already subject to FDA registration requirements as a drug product manufacturer. The imposition of an additional registration requirement would be redundant as there are already mechanisms and controls in place for these drug ingredients before they are used in the finished drug product.

7 Page 7 Research compounds and samples for forensic or other analyses that are not for human or animal use and not for sale and do not otherwise require special license (e.g,, pathogens) should be exempt from the FDA registration and border processes generally through filing of a new affirmation of compliance code submitted at the time of entry. 3. What information should commercial importers be required to submit as part of their registration? Unique manufacturing facility identity and the data currently required of commercial importers at the time of entry for targeting in PREDICT should continue to be required, supported, when needed, by commercial documents that the importer should have available for inspection. However, we believe that trusted importers should be relieved of this burden and be required to file, at the time of entry, an AOC affirming the import is covered by a trusted trader exemption, along with a unique manufacturing facility identifier. All importers, including commercial importers, should have documents available for submission detailing the product and lot imported, should that be needed. 4. What benefits and burdens might be created by requiring commercial drug importers to register with FDA? How can we minimize any possible burdens (e.g., through gradual implementation, exemption of certain commercial importers, use of other alternatives)? Commercial importers and importers should have the same benefits and burdens C. Section 714: Good Importer Practices 1. How might FDA structure the GIP regulations to avoid imposing redundant regulatory requirements on commercial importers that also are drug manufacturers and therefore would be subject to both the GIP and CGMP requirements? We believe that trusted importers, whether manufacturers or commercial importers, should only be required to file, at the time of entry, a trusted certified importer affirmation of compliance code (AOC) and the data indicated under Question #2. The task of eliminating redundancy should occur during the application and review process. Other importers should be required to file, at the time of entry, data now required for PREDICT processing. 2. Should the GIP regulations require commercial importers of drugs to establish drug safety management programs to ensure that imported drugs meet the requirements of the FD&C Act and the Public Health Service Act, as applicable? If so, what matters (e.g., procedures, personnel) should the GIP regulations require commercial importers to address in such programs? We believe commercial importers should be subject to the same or similar safety and security management protocols. 3. What drug safety management programs or other measures do commercial importers currently have in place to ensure that imported drugs are manufactured in compliance with applicable FDA requirements? How do these programs and measures differ for different types of drugs? Commercial importers and importers should have the same benefits and burdens.

8 Page 8 4. Should the GIP regulations include qualifications and training for personnel who perform GIP activities? If so, what qualifications and training should be required? We support the need for personnel training to perform Good Importer Practice (GIP) activities. GIP rules should mimic GMP s and, similarly, not be proscriptive. Training and qualifications need to be a function of the specific task to be performed. 5. Should the GIP regulations include a requirement for commercial importers to assess whether it is appropriate to import a particular drug from a particular foreign supplier? If so, what information on the drug and the supplier should the commercial importer be required to consider as part of this assessment? Commercial importers and importers have the same responsibilities to product quality assurance and patient safety and require the same oversight and control. 6. Should commercial importers be required to conduct activities to verify that a drug that is offered for import is in compliance with applicable U.S. requirements (e.g., the CGMP regulations) and are not adulterated under section 501 of the FD&C Act (21 U.S.C. 351) or misbranded under section 502 of the FD&C Act? If so, what supplier verification activities should commercial importers be required to conduct? Commercial importers and importers have the same responsibilities to product quality assurance and patient safety and require the same oversight and control. 7. Should there be different supplier verification or other GIP requirements for different types of drugs? Should there be different requirements for particular types of finished dosage form drug products that might be associated with different levels of risk (e.g., sterile injectables, drugs that require temperature controls)? If so, what should these requirements be? GIP regulations should include a requirement that the commercial importer have documented procedures on management of the specific risks associated with various types of products and scenarios. GIP regulations should not speak to the detail required in these procedures. 8. Should the GIP regulations require commercial importers to obtain a COA for each imported drug? Should such a requirement apply only to certain types of drugs or commercial importers? If commercial importers are required to obtain COAs, should the commercial importer also be required to conduct testing to verify the accuracy of the COA? GIP regulations should require the commercial importer to have documented procedures that ensure the safety and compliance of imported materials. GIP regulations should not speak to the detail required in these procedures. 9. Should the GIP regulations include specific requirements for drugs imported for export in accordance with section 801(d)(3) of the FD&C Act? If so, what should these requirements be? Drugs imported for export may not be subject to the same requirements as drugs imported for domestic consumption. Existing regulations address this topic. Drugs imported for export should be identifiable by an appropriate AOC code.

9 Page How should the GIP regulations reflect or incorporate the requirements concerning the standards for admission of imported drugs under section 801(r) of the FD&C Act? For example, should the GIP requirements include the adoption of procedures to ensure that the commercial importer submits the compliance information required under section 801(r) and the regulations implementing that section? If so, what procedures should commercial importers be required to follow to ensure that these requirements are met? GIP regulations should reference the requirements in 801(r). 11. Should the GIP regulations require commercial importers to take corrective actions when the drugs they import or offer for import are not in compliance with applicable U.S. requirements? If so, what actions should importers be required to take? Commercial importers should be required to address import issues in the same manner as currently required for manufacturer importers, including a requirement to have effective recall programs in place. 12. Should the GIP regulations include a requirement for commercial importers to list the drugs they import or offer for import? If so, what information should be required with listing? It is the responsibility of the importer (or commercial importer) to ensure that imported products are drug listed in accordance with the FD&C Act. GIP regulations should reference existing drug listing regulations. 13. What records should commercial importers be required to maintain under the GIP regulations? Drug supply chains consist of multiple links. Commercial importers should be required to maintain records that start with the quality tests last performed at the manufacturing source, proving efficacy and compliance with applicable cgmp s and corporate policies, and continuing to delivery to the importer or the first domestic buyer if goods are consigned to other than the importer. Importer records should also show control exercised over the supplier, through, for example audit schedules and outcomes. 14. What other matters, if any, should the GIP regulations address? The timing for enforcement of the GIP regulations should be determined for each importer, taking into consideration the effectiveness/appropriateness of its internal practices and procedures, as well as the risks associated with the types of materials imported. 15. How should FDA take into account differences among importers and types of imports, including based on the level of risk posed by the imported product, in determining reasonable time periods for commercial importers to come into compliance with the GIP regulations under section 714(d)(3) of FDASIA? In considering such differences, how should FDA determine the level of risk posed by an imported drug? FDA should develop levels of risk using an account based rather than dosage form or source approach. The same concepts as regards the trusted importer program should apply to risk based implementation times.

10 Page What benefits and burdens might be created by requiring commercial importers to comply with GIP regulations? How can we minimize any possible burdens (e.g., through gradual implementation, exemption of certain commercial importers, use of other alternatives)? Regulations applicable to commercial importers should be equivalent to manufacturer importers and compliance with GIP regulations should be required in the same manner as a matter of patient safety. Respectfully Submitted, Anthony Barone Director, Global Logistics Policy