Saturday, December 27, 2014
Draft US Senate Leglislation Minimize

Summary of the HELP discussion draft of the Drug Supply Chain Integrity legislation, dated March 16, 2012

The Senate Health, Education, Labor and Pensions Committee recently released a discussion draft of legislation titled Drug Supply Chain Integrity. The working group that developed this discussion draft includes Senators Harkin, Enzi, Bennet, Burr, Grassley and Whitehouse.  It includes several new concepts that have not been proposed in earlier versions of draft drug safety legislation along with concepts that have previously been introduced.  These core concepts are summarized below.

The significant new features in this proposal include:

  1. Qualification and use of 3rd party auditors to supplement the FDA inspectorate; 
  2. Establishment of a risk based inspection schedule that eliminates the current statutory requirement for biennial GMP inspections;
  3. Options for “paper-based” inspections conducted by FDA at their offices, without actually visiting the manufacturing site;
  4. Application of these requirements outside of the United States. 

This working draft also includes requirements that have been addressed in prior legislative proposals on supply chain, including:

  1. Registration of domestic and foreign sites;

  2. Development of an FDA database of these sites capable of sharing information with other FDA databases;

  3. Consequences of failure to permit or delay inspections;

  4. Exchange of information with other regulatory agencies;

  5. Inclusion of the management of risk posed by raw materials within the concept of CGMP;

  6. Standards for imported drugs and the destruction of detained drugs;

  7. Responsibility to notify the FDA about potential instances of drug counterfeiting;

  8. Enhanced criminal penalties for counterfeiting and intentional adulteration;

Details of New Features

  1. Approximately half of the proposed bill addresses the qualification and use of 3rd party auditors to augment the FDAs inspectorate. Inspectorates from other regulatory agencies, for example the European Medicines Agency (EMA), can qualify as 3rd party auditors. Third party auditors are not intended to replace FDA inspectors but rather appear to supplement their functions.  The term used for their activities are “drug safety audits”, rather than CGMP inspections.  These “audits” will be conducted to assess compliance with the FD&C Act, rather than the GMPs.  The 3rd party auditor must agree to “issue a written and, as appropriate, electronic, certification regarding compliance…to accompany each drug shipment for import into the United States...” . Third party auditors will be recertified on a periodic basis and a process for removing their certification will be established.  This program appears to be similar to3rd party inspections in for medical devices.   

  2. The discussion draft proposes a new approach to risk-based inspection planning that removes the current statutory requirement for biennial GMP inspections.  Such planning does not differentiate between domestic inspections and foreign inspections.  The factors to be considered in determining the risk-based frequency of inspections include an establishment’s compliance history, history and nature of recalls from the site, inherent risk based on the type of manufacture, certifications and “any other criteria deemed necessary and appropriate by the Secretary…”  The ability to implement this approach depends on successful implementation of an electronic database to store establishment registration information discussed in the following section of this article. 

  3. FDA appears to allow for the option of a “paper-based” inspection based on documents requested by the FDA and supplied by the firm. The documents may be provided to FDA in either electronic form or as paper documents.  Any expense incurred in providing these documents to FDA will be responsibility of the firm. Many documents would likely be provided electronically to FDA because transfer of original paper documentation outside of company sites may be prohibited by firms’ procedures.   

  4. These requirements are meant to apply to jurisdictions outside the United States if the “article” regulated under the FDC Act “…was intended for import into the United States or if any act in furtherance of the violation was committed in the Unites States.”  This appears to cover both drugs and devices.   


Details of Features Previously Addressed

  1. Both domestic drug manufacturers and foreign drug and device manufacturing sites are required to register with the US and to re-register annually.  Domestic drug sites must provide the name, place of business, unique facility identifier for each establishment, and e-mail address of a contact person.  The name of each importer and drug excipient manufacturer must be provided with a unique facility identifier for each such establishment and an email for the contact person.  Foreign drug manufacturing establishments must register via an electronic system and provide similar information to that required of domestic manufacturers in addition to the name and contact information for the US agent.  Foreign device establishments must provide the name of the US agent, the name of each importer of the device and the name of the person who offers the device for import into the US. 

  2. The FDA is required to develop and maintain an electronic database of the registration information from 1 above.  The database must be able to communicate with others within the FDA organization. The information in the registration database will be used to implement risk-based inspection planning.

  3. The Department of Homeland Security “shall” refuse admission of articles into the US “manufactured…or held” at sites that did not permit or that delay a GMP inspection.  Further, the Department also will have authority to destroy drugs that “has reasonable probability of causing serious adverse health consequences or death to humans or animals….”  Regulations must be implemented to provide the opportunity for informal hearings that would occur after the destruction of material valued at less than $2,000 and before the destruction of materials valued at more than $2,000.  Restitution may be provided if it is later determined that the materials were wrongfully destroyed.  

  4. The Secretary of Health and Human Services may enter into Memoranda of Understanding with a foreign government for the purposes of sharing information.  The foreign government must be able to adequately protect trade secret information.  This responsibility may be delegated from the Secretary only to the Commissioner of the FDA.  Information that FDA has deemed should be kept confidential will not be shared with foreign governments except in the case of a court order.  

  5. The discussion draft incorporates into the CGMPs the concept that manufacturers are responsible to know and manage the risks potentially posed by their raw material suppliers.  The details of how this should be operationalized are not elaborated on in the draft.

  6. Imported drugs must be accompanied by specific information in order to be permitted entry into the US.  The importer must submit information “…demonstrating that the drug complies with applicable requirements of this Act.”  This requirement would place the burden on the importer for ensuring that product is compliant with CGMPs.  It is in contrast to the current situation where FDA must permit import of drugs in the absence of information regarding their GMP compliance status unless FDA can establish they were produced in a manner non-compliant with CGMPs.  Several options for information that may be provided to meet this requirement include, but are not limited to, the number associated with an NDA/DMF/IND/ANDA application, facility registration along with the unique identifier, certification demonstrating a satisfactory inspections, and compliance with import and export regulations.  Further, if the manufacturer employed 3rd party auditors, information must be provided regarding their identification and specifics of their evaluation of the site. Rulemaking will be necessary to establish the specific requirements.

  7. A person required to register an establishment as a drug manufacturer and a person engaged in wholesale distribution of drug may be required to notify FDA regarding loss or theft of a drug or drug counterfeiting when i) a “substantial” loss or theft of a drug occurs, or ii) when it becomes known that the drug is being counterfeited and is either in commerce in the US or is being imported into the US.

  8. The discussion draft provides for increased criminal penalties for counterfeiting of drugs, up to 20 years in prison and / or fines of not more than $4,000,000.  Intentional adulteration will be subject to not more than 20 years in prison and/or a fine of not more than $1,000,000.




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