RPI Introduces CMC Services

RPI is pleased to introduce our experienced team of Chemistry, Manufacturing and Controls (CMC) experts.

RPI can provide you with comprehensive technical, compliance and writing support services for all of your CMC requirements at all stages of drug and biopharmaceutical development. We have extensive experience in CMO selection and management for small-molecules and biologics for many types of drug substances and all forms of drug products including aseptic fill and finish. Specialty areas include protocol development and reports for the validation of analytical assays, utilities, equipment and processes, OOS investigations, deviation reporting, specification justification stability (including formal stability shelf life projection reports) and development histories. We also offer GMP Quality Assurance and compliance support appropriate to the stage of drug development including SOPs, Test Methods, and facility and laboratory audits and can assist you in preparing for a pre-approval inspection.

Read more about our CMC experts below:

Ramon Burns, Ph.D.
Ramon has over 25 years’ experience in the development, manufacture and control of pharmaceutical products. He started his career at Syntex in parenteral product development and held pharmaceutical and analytical chemistry management positions at Collagen Corporation and Celtrix Pharmaceuticals. Ramon started consulting in 1995 and has worked on a wide variety of projects since involving cost effective, high quality report preparation, data analysis, and scientific or manufacturing process troubleshooting. Ramon is a six-sigma black belt whose technical expertise ranges over assay validation, stability (including formal stability shelf life projection reports), specification justification, and OOS/OOT auditing/root cause analysis. Specialized writing project completed include process descriptions, technology transfer reports, CTD section writing, development history reports, and method comparability reports. Ramon holds a BA degree in Biophysics from the University of Pennsylvania and a PhD in Chemistry from the Massachusetts Institute of Technology.

Robert Lopez
Robert has over 30 years experience in the development, manufacture and registration of biopharmaceuticals. His career started in medical devices and he subsequently held director level positions in a number of biotechnology companies including Genzyme, Genetics Institute, Celtrix and Telik. As a consultant Robert has specialized in CMO project management for biologics and aseptic products, performing activities such as proposals and contracts, budgets, project timelines, SOP and batch record generation and review, batch release, clinical supply logistics, Person in the Plant and on the floor Manufacturing Quality. Robert holds a BS in Medical Microbiology from San Jose State University.

Malcolm McKay, Ph.D.
Malcolm has over 30 years of GXP Compliance and Regulatory Affairs experience in the pharmaceutical industry. He started his career at Abbott Laboratories and later held senior Quality Assurance and Regulatory Affairs positions at a number of small-to-medium companies including Triton Biosciences, Berlex Biosciences, Celtrix Pharmaceuticals, COR Therapeutics, Cell Genesys, InterMune and Vivus. His strategic, tactical and technical experience comes from working with small molecules, peptides and biologics for a variety of dosage forms that involved the successful submission of dozens of CMC dossiers for INDs, BLAs, NDAs and MAAs. Malcolm holds a BS degree in Biology from Portsmouth University and a PhD in Biochemistry from King's College, London.

FDA Draft Guidance on Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications

In July 2014, FDA issued a revised draft guidance for industry titled “Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications.” The draft guidance closed for comments on September 23.

Twenty-four months after this guidance document is finalized, the content of certain submission types must be submitted electronically via the Electronic Submissions Gateway (ESG) and formatted according to the eCTD specifications outlined in this guidance.

These requirements apply to all submissions under section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which include submissions under section 505(b) (new drug), 505(i) (clinical trial), or 505(j) (generic drug) of the FD&C Act, and under section 351(a) (biologic) or 351(k) (biosimilar) of the Public Health Service Act (PHS Act). These include:

• Certain INDs;
• NDAs;
• ANDAs; and
• Certain BLAs. 

Submissions that are not submitted electronically and electronic submissions that are not in the format specified in this guidance document will not be filed, unless exempted from the electronic submission requirement. FDA will exempt the following types of submissions:

• All submissions regarding devices that are regulated by CBER as biological products under section 351 of the PHS Act;
• Noncommercial INDs; and
• Existing master files previously submitted in non-electronic format.

This draft guidance is a revision of the draft guidance previously issued in January 2013. When finalized, it will supersede the guidance issued in June 2008 titled “Providing Regulatory Submissions in Electronic Format — Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications.”

Contact RPI for assistance in meeting FDA’s new electronic submission requirements.

EU Clinical Trials Regulation

On May 27, 2014, the Clinical Trials Regulation was published in the Official Journal of the EU (OJEU). It will replace the existing EU Clinical Trials Directive and streamline the authorization process. The legal form of a Regulation ensures that EU Member States, in authorizing and supervising the conduct of a clinical trial, do so on the basis of identical rules. Barring IT issues, it will apply starting from May 28, 2016.

The key provisions include:

• Applicants will submit a single application for the authorization of a clinical trial via a single EU portal. Applications will receive a single assessment outcome, regardless of the number of EU Member States concerned.
• The European Commission will have the possibility to conduct controls in EU countries and third countries to make sure rules are being properly supervised and enforced.
• Certain clinical trials determined to be “low-intervention,” such as those comparing already authorized medicines, will be subjected to lighter regulatory requirements.
• Clinical trials conducted outside the EU but referred to in a clinical trial application within the EU must comply with regulatory requirements at least equivalent to those in the EU, including rules on transparency.
• Member States will have the possibility to stop any clinical trial which they consider could endanger the heath of the participants.

For further assistance with the EU clinical trial authorization process, contact RPI.

RPI Presenting at VxP Pharma Seminar in November 2014

Donna Kato of RPI and Barry Calvarese, Ph.D. are featured speakers on "Essential Steps to Successful IND Submissions" at the VxP Pharma Seminar: Strategies for Success in Virtual Drug Development.

The upcoming seminars are scheduled for:

• November 11th: San Diego, California | La Jolla Hilton Torrey Pines
• November 12th: South San Francisco, California | Embassy Suites
• November 13th: Palo Alto, California | Crowne Plaza Hotel

Register to attend on the VxP Pharma website.

FDA Final Rule and Draft Guidance on Orphan Drug Designation

A final rule amending the 1992 Orphan Drug Regulations became effective on August 12, 2013. The main change from the proposed rule was to add the definition of “orphan subset”.  In particular, “Orphan subset of a non-rare disease or condition (‘orphan subset’) means that use of the drug in a subset of persons with a non-rare disease or condition may be appropriate but use of the drug outside of that subset (in the remaining persons with the non-rare disease or condition) would be inappropriate owing to some property(ies) of the drug, for example, drug toxicity, mechanism of action, or previous clinical experience with the drug.” Additional changes include:

• Removing the language in the proposed rule that, to demonstrate clinical superiority, the drug must provide safety and effectiveness comparable to the approved drug
• Clarifying that a designation request need include only ‘relevant’ in vitro laboratory data, as well as data from ‘clinical experience’ with the drug in the rare disease or condition
• Stating that FDA’s publicly available posting of designated drugs will include whether a drug is no longer designated if the drug loses designation
• Clarifying that the scope of orphan exclusive approval is limited to the indication(s) or use(s) for which the designated drug is approved
• Clarifying that a designated drug that is otherwise the same as a previously approved drug receives 7-years market exclusivity upon approval only if the sponsor of the second-in-time drug demonstrates upon approval that its drug is clinically superior to the previously approved drug

A draft guidance published in April 2014 describes procedures for meetings with the Office of Orphan Products Development (OOPD), including timing:

• OOPD will aim to respond to a request for an informal or formal meeting within 5 working days of receipt. Before scheduling the meeting, OOPD may request a brief list of questions that the stakeholder hopes to have answered.
• If a formal meeting is scheduled, OOPD should receive a meeting package at least 2 weeks before the meeting. If OOPD fails to receive a meeting package on time, OOPD may postpone the meeting and work with the stakeholder to reschedule.
• If meeting minutes are warranted, the stakeholder should provide a draft of summary meeting minutes within 15 working days after the meeting.

For further assistance on preparation of orphan designation applications, contact RPI.

FDA Draft Guidance on Pediatric Study Plans

The FDA Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, requires that the sponsor of a drug subject to the Pediatric Research Equity Act (PREA) submit an initial pediatric study plan (PSP) early in the drug development process. The intent of the PSP is to identify needed pediatric studies early in drug development and begin planning for these studies.

A draft guidance published in July 2013 specifies the timing of a PSP submission:

• The sponsor must submit the initial PSP before the submission of the required assessments and no later than 60 calendar days after the end-of-phase 2 meeting.
• In the absence of an end-of-phase 2 meeting, the sponsor should submit the initial PSP as early as practicable but before the initiation of any phase 3 studies, or any combined phase 2 and phase 3 study.
• If a phase 3 study, or a combined phase 2 and phase 3 study, will not be conducted, the sponsor should submit the initial PSP no later than 210 calendar days before the submission of a marketing application or supplement.

A sponsor should submit the initial PSP to its Investigational New Drug (IND) Application. In cases when there is no active IND for the drug, but the sponsor expects to include a phase 3 or combined phase 2 and phase 3 study, the initial PSP should be submitted as a pre-IND submission. In this situation, FDA encourages sponsors to schedule a pre-IND meeting before submission of the initial PSP.

For assistance on preparation of Pediatric Study Plans, contact RPI.

FDA Guidance on Providing Regulatory Submissions in Electronic Format — Receipt Dates

FDA Guidance on Providing Regulatory Submissions in Electronic Format — Receipt Dates

In February 2014, the FDA issued a guidance to assist sponsors, applicants, and others making regulatory submissions in electronic, paper, or hybrid format to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).

The guidance eliminates the 4:30 PM cut-off for electronic submissions received through the electronic submission gateway (ESG) Monday through Friday. Electronic submissions submitted up to 11:59 PM will now be assigned a receipt date corresponding to the same day of submission.

The FDA states that a regulatory submission’s receipt date is the date on which the submission is deemed to have arrived at the FDA. The receipt date may be used to determine important regulatory milestones, such as the end of the 30-day safety review cycle and the review performance goal date.

A paper submission is assigned a receipt date corresponding to the day on which it physically arrived at the appropriate receiving unit of the FDA center designated to review the submission, while the office is open for business.

Contact RPI to find out how your company can use electronic publishing to streamline the FDA submission process.