Aug 14, 2013

Review of FDA Guidance "Codevelopment of Two or More New Investigational Drugs for Use in Combination"


by Seth A. Mailhot, Special Counsel, Sheppard Mullin Richter & Hampton LLP

On June 14, 2013, FDA issued the Guidance “Codevelopment of Two or More New Investigational Drugs for Use in Combination.”  The guidance discusses FDA’s recommendations for developing an entirely new combination therapy where none of the drugs to be used in combination have been previously developed.  FDA notes in the guidance that the recommendations do not apply to combination therapies involving previously developed drugs, or the combination of a new drug with a previously developed drug.  While codevelopment has generally been centered in oncology and infectious disease, FDA’s guidance is intended to address codevelopment from a high-level, making it applicable to other diseases.

The complexity of certain diseases, such as cancer, cardiovascular disease, and infectious diseases, presents unique challenges to medicine.  As scientific understanding of pathophysiological processes has increased, development of combination therapies has become increasingly possible.  The potential benefits of combination therapies include improving treatment response by directing treatments at multiple therapeutic targets, minimizing development of drug resistance, and countering drug side effects and adverse events.

Elements of Effective Quality Agreements


by Steven Sharf, President and Principal Consultant, GMP Concepts

Many GxP professionals are already familiar with the expectation of FDA and the requirement in the EU to have quality agreements with third parties and suppliers.  Throughout this article, I will define what a quality agreement is, when one is needed, the 24 basics that factor into this critical document, and some things to avoid when drafting one.  Finally, I will discuss alternate means of communicating quality expectations when a supplier will not agree to enter into a full quality agreement. 

What is a quality agreement?
A quality agreement is a contract between two parties that defines the role of each in the manufacture, packaging, testing, holding, and/or distribution of product to the marketplace.  It is through this document that both the sponsor (contract giver) and the contractor (contract receiver) know such things as who is responsible for investigating complaints; who is responsible for initiating a recall; what is the expectation for completing investigations; who is responsible for releasing material; and who are the key contacts within each organization when a quality issue arises.  While there are many elements to a robust quality agreement, I feel the most important is defining the role of each company in communicating change.  The quality agreement should be very clear as to the types of changes that require notification (this would apply to contractor-driven changes as well as those initiated by the sponsor), the timeframes for communicating and implementing changes, and the required approvals for change.  The amount of detail that goes into a quality agreement will be dependent on the companies involved (mainly on the sponsor’s requirements), the type of work being performed and the relationship between the sponsor and the contractor.

Building a Quality Plan for Implementing EN ISO 14971:2012


by Robert Packard, Regulatory Consultant, MedicalDeviceAcademy.com

On May 16 of 2012, the European Committee for Standardization (CEN) approved a revised European National Standard for medical device risk management: EN ISO 14971:2012. There were no changes to the main body of the Standard (i.e. – Clauses 1 through 9). Instead, the revised European National (EN) version identifies seven deviations in Annex ZA, ZB, and ZC with respect to the intent of the MDD, the AIMD, and IVDD respectively. Those seven deviations are:

1. Treatment of Negligible Risks
2. Discretionary power of manufacturers as to the acceptability of risks
3. Risk reduction “as far as possible” (AFAP) vs. “as low as reasonably practicable” (ALARP)
4. Discretion as to whether a risk-benefit analysis needs to take place
5. Discretion as to the risk control options/measures
6. Deviation as to the first risk control option
7. Information of the users influencing the residual risk

The following sections of this article provide recommendations for how to update your existing risk management procedure and processes to ensure compliance for CE Marked medical devices.