New Draft Guidance on Best Practices for IND Communications Between Sponsors, FDA.

Investigational New Drug Application (ING) sponsors contacted the Food and Drug Administration (FDA) in various stages of drug development today will have a new set of new consulting practices of his meetings with the FDA developed guidelines published Friday.

Communications between the FDA and industry are often the opportunity to share information on clinical trials and cirtical agency for advice on the design of clinical trials, the selection of the dose, clinical studies requirements and manufacturing problems and installation.

It is important that the agency industry interactions "are carried out effectively and consistently, with a clear, concise and timely communication," says FDA announcing management.

Type of meeting

Milestone meetings include pre-IND, end of phase 1, the end of phase 2, and pre-NDA / BLA (demand for new license applications for drug / biological) meetings.

Pre-IND meetings, which can prevent problems from Clinical suspension, can be valuable for understanding the proof of concept and to initiate a dialogue for the development of drugs to debut the company develops a complete IND submission.

"The FDA encourages sponsors to request a pre-IND meeting to: a drug not previously approved / accredited, a new molecular entity (NME), a marketing application planned for presentation in (b) (2) 505 drugs regulation which is essential for public health that has a plan of development of efficient and effective drugs (for example, the fight against terrorism), drugs with substantial early development was US development program of properly planned and well-controlled drugs and to support human factors testing new indication, "said the agency.

Under certain circumstances, it may be granted a pre-IND meeting face-to-face meeting or teleconference. Pre-submission meetings are useful to familiarize examiners FDA "with the format and content of the intended application, including labeling activities and risk management (if any), presentation and organization of data, structure data set, the acceptability of the presentation of the data and the expected filing date. "

They also aim to discover other important issues such as the identification studies to establish safety and efficacy, to discuss the state of pediatric studies and discuss the methods or results of tests appropriate statistical analysis issues.

FDA says "encourages sponsors to ask Meeting / BLA planned pre-NDA for all marketing applications, including applications to be examined under the PDUFA V Program strengthens transparency NDA review and Communication NME original Blas".

Context

The FDA and sponsors have different views of what constitutes the IND-development phase. From the perspective of the FDA, the agency said the IND stage extends the time of the first communication concerning IND (including a meeting request pre-IND) submission of a marketing application.

From the perspective of the developer, he said the FDA, drug development is not limited to the IND stage, as it also includes drug discovery and preclinical compound to an IND filing work, including clinical trials in other countries outside the IND.

Each year the sponsors and FDA are involved in thousands of formal and informal communications, including meetings and teleconferences during the IND phase..

At the request of the sponsor, the FDA, if possible, provide advice on specific issues IND.
"Examples include providing advice on the adequacy of the technical data to support an experimental design, the design of a clinical trial, and if the research proposals are likely to produce data and information necessary to fulfill the requirements of a marketing application . Because of the complexity and importance of the documents submitted to IND vary by therapeutic indication and stage of development, examination divisions retain the flexibility to determine the scope of the review and commented to each presentation, "the FDA says

For drugs developed through accelerated programs, such as expedited processing of advance programs and sponsors receive "more intensive attention in the program of development of effective drugs with increased interactions and communications with the FDA, including meetings".

Interactions

The regulation of Division Project Manager (RPM), which has a full knowledge of the drug and its regulatory history, is the main point of contact for communications between developers and IND by the FDA throughout the life cycle of drug development.

The RPM is the main contact to facilitate rapid resolution of technical, scientific and regulatory conflicts or problems of communication between the sponsor and the review team, the FDA said.

During drug development that there are circumstances where it is appropriate for sponsors to contact the project managers who are not directly RPM division of FDA review in the FDA Center for Drug Evaluation and Research Drug (CDER). The other project managers include:

1. CDER Office pharmaceutical quality regulatory project managers of the companies, which manage meeting requests, regulatory submissions and other information related to chemistry, manufacturing and controls, including installation issues and product quality;

2. CDER Office managers surveillance and regulatory certainty Epidemiology Project, managing sponsorship applications for review of proper names; and 3. Formal Dispute Resolution Manager of CDER project, which handles requests to sponsor the resolution of disputes / or science and medicine that can not be solved at the level of the division.

CDER and the FDA Center for Biologics Evaluation and Research (CBER) say they "are aware that some sponsors want to communicate directly with their examiners assigned to IND" but as "communications are strongly discouraged and can not communicate Sponsors directly examiners FDA. It is essential that requests for sponsorship be sent notification of dividing RPM to ensure that applications communicate and properly considered by the members of the review team including supervisors, if necessary " says the FDA.

Council sought

Types table a drug sponsors will be applied during the development life cycle of drugs can vary depending on the experience of the promoter and include topics such as:

1.  Regulatory (eg, plans for the filing of property names, plans to postpone or waive specific studies, development plans with other centers of the FDA (for example, the Center for Devices and Radiological Health) for products combination), the applicability of a crash program;
2. Clinical Statistics / (eg, plan clinical trials to support the efficacy, the validity of the results and evaluation criteria, test format, designs enrichment);
3.  Security issues (eg security identified in non-clinical studies and initial clinical trials, the overall size of the security concerns of databases for specific populations, pharmacovigilance plans after approval, evaluation strategies and risk mitigation plans, studies on issues of human factors related to the assessment of potential abuse);
4. Clinical Pharmacology and pharmacokinetics (eg, dose selection, use in specific populations, drug interactions);
5. The non-clinical pharmacology, pharmacokinetics and toxicology (eg, genetic toxicology, reproductive toxicology and development, carcinogenicity, mechanism of action); and
6. The quality of the product (for example, studies of the proposed shelf life and stability, delivery systems, characterization of the drug substance / product, ease compliance with good manufacturing practice, the comparability of the batches used in tests clinical and commercial lots); and a child development plan and the proposed dose.

Complex issues involving the interpretation of rules and regulations, or the implementation of the policy of the new FDA existing circumstances, may require vetting and additional response time, according to the FDA.

Change of employment

The orientation will be organized by new drug application (IND) sponsors, although the FDA said the guidance to communications or consultation of trade organizations in the industry, consumer organizations and patient advocacy, other government agencies or others does not apply stakeholders who do not pursue a development program IND.

And for companies that do not meet the FDA says drug development later, may be adversely affected by the delay or failure of sponsors to meet the FDA, if the response time of the FDA can also be affected if the team negatively experiments review "an unexpected change in work priorities or team personnel. In these cases, the project director of the FDA sponsors try to keep abreast of changes in the estimated timing response."

If sponsors are delays in the FDA's response is obtained, the FDA advises the sponsor contact (sequential):

1. The director of the project appropriate FDA generally reviews the RPM division for a status update after the scheduled time (for example, time limits described in MAPP) to the response of the FDA's happened;
2. The director of the project appropriate FDA generally reviews the RPM division for a status update after you have passed the estimated response time (eg date FDA-response estimate previously communicated to the sponsor);
3. Next level supervisor project manager at the FDA for appropriate assistance to provoke a response from the project manager; and division or competent officials desktop management to help get a response from the project manager; or 
4. CDER or CBER mediator for help to get a response from the project manager.

Using secure e-mail can allow seamless communication between the FDA and sponsors, although the agency noted that "it is not a substitute for formal presentations (eg new IND and amendments); official tenders must be submitted to the CRD respective center (of paper) or through the electronic portal, as appropriate. "

Communication via email unsecured FDA can not include confidential business information, in particular regarding trade secrets, manufacturing or patient information to sponsors must establish secure email with the FDA to allow Informal communications may include confidential business information.