John Webb Consulting Services - Services Provided

By: John Webb Consulting Services  09-12-2011
Keywords: Product Development , Regulatory Agencies

Services Central: Working Together To Avoid Regulatory Delays

John Webb Consulting Services Inc. is committed to providing high quality, value-added services to our clients. Our commitment to quality is based on our scientific expertise and years of regulatory experience and on the adoption of a partnership role with the members of your project teams to ensure optimum communication and regulatory strategies that work.

  • We advise on the chemistry, manufacturing and controls (CMC) part of submissions, including where appropriate, preparation of high quality CMC summaries (QOS) for IND's, New Drug Submissions (NDS), Supplemental New Drug Submissions and Notifiable Changes. More economically, we can work with the CMC summary prepared within your company and upgrade it, if necessary, to meet the expectations of the Bureau of Pharmaceutical Sciences (BPS). In addition, we pinpoint the issues that could delay regulatory approval and recommend solutions, so that clients can proactively address these problems. We do this whether we are working with the CMC summary prepared within your company or when we prepare the summary.
  • With implementation of the CTD, there may be expectations that CTD-based drug submissions prepared in Europe or the U.S. will encounter fewer problems when the CMC part of the submission is evaluated in Canada by BPS. However, there are still significant differences in approach among regulatory agencies with respect to collection/interpretation of data and establishment/justification of some specifications, despite the harmonization achieved thus far by ICH. Nevertheless, if the Canadian branch of a multinational company becomes involved at an early stage in the preparation of drug submissions, we can assess the CMC content as the submission is being assembled and provide early feedback on problem areas to ensure that Canadian requirements are met. Ensuring that submission content is 'right' at the time of filing is the best way to avoid delays during the regulatory review process.
  • One way to ensure a 'clean' submission is to have us prepare an expert assessment on the CMC part of your new drug submission. A 'Canadian style' expert report, when properly done, is not really a summary of the submission; rather, it is a critical assessment in which issues likely to be of concern to the Canadian regulators are discussed. The potential concerns are either resolved in the discussions or remedies are suggested. In our experience, the most time/cost efficient approach is to have us prepare both the CMC summary and an expert assessment in parallel, since the ground work is much the same for both. At the present time, an expert report is best used internally by the client to gain a heads-up on issues that are likely to be of concern to BPS. Depending on lead time available, unresolved issues raised in the expert report can either be dealt with prior to filing the submission or addressed while the submission sits in queue. Either way, the extensive delays (typically, months), associated with receiving a Notice of Noncompliance (NON) because of CMC issues, can be avoided, as can delays arising from major issues in a clarification request, for which there may be insufficient time to respond within the limited time line.
  • For inhalation products, in addition to preparation of the CMC summary and/or expert reports, we also offer advice in connection with product development and different requirements of the various regulatory agencies. In particular, there are striking differences between BPS/EMEA requirements for dose uniformity and particle size testing and those of the FDA (see discussions available on our Downloads page). A company intending to market a product in both Canada and the U.S. needs to be aware of these differences early in product development. Accordingly, we provide analysis and advice on how to integrate in vitro testing protocols into the clinical development program to ensure that clinical trial batches are well characterized and, eventually, that limits on key attributes in the finished product specifications are properly qualified. For MDIs and DPIs, where there is still much debate on in vitro testing, it is important to develop thorough, scientifically justified testing protocols very early in product development if significant delays are to be avoided down the road, when the marketing application is under regulatory review. We would like to assess the in vitro testing protocols prior to the filing of the IND's, but if brought in at a later stage in development, we can still assess the existing protocols and advise on whether additional testing should be done as an interim measure to address potential deficiencies that are likely to be raised at some point by a regulatory agency.
  • In the unfortunate event of receipt of a deficiency letter (in Canada - Notice of Deficiency (NOD), NON, clarifax), we provide in-depth analysis of the CMC issues and solutions that will satisfy the regulatory authorities. With the time restrictions for responses to deficiencies and the possibility of withdrawal of the submission, it is important to get the responses right. However, it is preferable not to lose the time, including queue time, associated with responding to a deficiency letter, by ensuring that there are no significant deficiencies in the original submission.
  • For submissions for solid oral dosage forms, the relationships between physicochemical properties, such as solubility and particle size of the active and the dissolution characteristics of the product, on the one hand, and permeability and bioavailability, and ultimately, safety and efficacy, on the other, require a more integrated approach in the evaluation of submissions. We ensure that the relevant parts of the Biopharmaceutics Classification System (BCS), SUPAC and ICH guidances are applied, to satisfy the concerns of the regulatory agencies.

Keywords: Product Development , Regulatory Agencies

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