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ers, and their quality systems and sources. Often this information is critical and proprietary to the supplier and not likely to be shared. The parties need to create mechanisms for the exchange of relevant information that protects both parties. Non-disclosure agreements, third party exchanges of information, i.e. through independent consultants or groups, password protected databases, use of Drug Master Files, or other mechanisms should be considered. • Timing. In view of FDA’s strong recommendation that Quality Agreements be separate from Master Service Agreements, and also be more detailed, the entire supply contract negotiation process will be extended. Additional time should be factored into the timeline for this part of the process, and establishment of a company policy precluding the interim or short-term use of any supplier that does not have a Quality Agreement should be considered. • Transparency about Filings. Especially in partnerships involving new product filings or supplements, it is important to
ensure that the supplier is kept up to date on filing developments and modifications so that there can be credible communications with FDA during pre-approval or other inspections and transfer of information into filings; failure to ensure all parties have the same information can cause misstatements to FDA and resulting data integrity concerns, failing inspections, and delayed or rejected approvals. Similar early information exchange is necessary by the supplier about changes it makes which may impact Owners’ filings. • Use of Third-Party Auditors to Qualify Suppliers. The parties must agree on whether, and the extent to which, they will rely on third party auditors, and who the auditors will represent. Suppliers often offer to Owners audits done by a third party paid for by the Supplier. This obviously raises potential conflicts of interest, and can result in significant gaps. For example, the significant peanut recall in the US that has now resulted in criminal action against the peanut supplier involved the reliance by many cus-
tomers on GMP audit reports conducted by third-party auditors hired by the supplier. • Alternative Suppliers. Many Owners have not made adequate preparations for alternative suppliers if there is a serious GMP deficiencies with a supplier. This can result in continued use of a supplier notwithstanding serious issues, or potential disruption of the business. Therefore, qualifying alternative suppliers or having redundancy is necessary for critical suppliers. • Diligence. Both Owners and suppliers must be willing to dig deep into their sub-suppliers, and ask hard questions about history, experience, and performance, and demand documented evidence of quality operations.
Conclusion
Supplier quality is the new frontier. Supplier quality issues should be front and center for review and enhancement in all compliance and quality plans to avoid serious regulatory enforcement actions and business disruption, in 2013 and beyond.
1
See letters to Joseph Jimenez, Novartis International AG, Basel, Switzerland, from FDA, CDER, dated Nov. 18, 2011, available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm281843.htm; Dr. Karl-Ludwig Kley, Merck KGaA, Darmstadt, Germany from FDA, CDER, dated December 15, 2011, available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2011/ucm291672.htm; Oliver Charmeil, Sanofi, Paris, France, from FDA, CBER, dated July 12, 2012; available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm312929.htm; and Dr. Gerhard Gigl, Boehringer-Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany, from FDA, CDER, dated May 6, 2013 available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm352325.htm.
2
See Draft Guidance for Industry, “Contract Manufacturing Arrangements for Drugs: Quality Agreements,” Food and Drug Administration (May 2013) available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM353925.pdf.
3
See Food and Drug Administration, Guidance for Industry, Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, available at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129098.pdf.
4
See ICH Harmonized Tripartite Guidelines, Good Manufacturing Guidelines for Active Pharmaceutical Ingredients Q7 (2000), available at http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html.
5
EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Chapter 5 (Production), sections 26-28 (Jan. 2012). (“Changes were also introduced in sections 26 to 28 on the qualification of suppliers in order to reflect the legal obligation of manufacturing authorization holders to ensure that active substances are produced in accordance with GMP. The changes include supply chain traceability”).
6 7 8 9
See ICH concept paper on updating QA7 document available at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/Q7_IWG_Concept_Paper.pdf See Request for public consultation on Rule Governing Medicinal Products in the European Union, Good Manufacturing Practice, chapter 5, Production, dated 17/01/2013 available at http://ec.europa.eu/health/human-use/quality/developements/index_en.htm. See United States Pharmacopeia, Drug Substance Verification Program (2007) available at http://www.usp.org/sites/default/files/usp_pdf/EN/support/pivpparticipantmanual.pdf. See International Pharmaceutical Excipient Council (IPEC) of Europe and America, Good Manufacturing Guide for Pharmaceutical Excipients (2006).
10 See Rx- 360 Consortium, an International Supply Chain consortium at www.Rx-360.org.
LMG LIFE SCIENCES 2013
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