Nobuo UEMURA 04/16/2010
Foreword
In mid-February I moved to the United States Pharmacopeia (USP) secretariat office as a first visiting scientist of USP General Chapter team from Japan and a liaison official of MHLW/PMDA ("Ministry of Health, Labour and Welfare" and "Pharmaceuticals and Medical devices Agency").
Under the international harmonization activities of pharmacopeias, MHLW/PMDA(Japanese Pharmacopoeia secretariat : JP) are participating in the Pharmacopeia Discussion Group meeting (PDG) with USP, EP(European pharmacopoeia) and IP(International Pharmacopoeia), and during this discussion they consider the USP text by comparison with the JP.
But by this time the USP's current activities and future aiming are not so familiar even to the Japanese Regulatory Authorities and Experts in the field of pharmacopeia.
Therefore in this first report from Washington D.C. Metro Area I briefly present the USP's history and current activities.
In addition, since I observed several FDA Advisory Committee meetings during my staying period, this report also includes how these Advisory Committee meetings are going.
However this report is my personal views and opinions, and it does not necessarily represent the formal position of MHLW, PMDA, FDA and USP.
1. USP - History and Role
The United States Pharmacopeia (USP) means a publication (book) of public pharmacopeial standards which has more than 4000 drug monographs and standards. At the same time the word "USP" is a name of the secretariat organization for the USP standard setting and publication.
The USP founded in 1820; 11 delegates of state societies of medicine attended, and USP created a system of standards, a system of quality control, and a national level formulary. Only 217drugs that met the criteria of most fully established and best understood were admitted in the first edition.
In 1830 the Committee of Revision was created by seven members, and revisions started at 10-year intervals. In 1848 Federal legislation recognized the USP as an official compendium, and in 1906 federal Pure Food and Drugs Act recognized the USP and National Formulary(NF) as official standards.
In 1938 the Food, Drug, and Cosmetic Act was established, and FDA approves drugs for safety before marketing. At this moment the USP standards were recognized as official, and these standards are enforced by FDA.
From 1942 USP was published every 5 years, and from 2002 is published annually.
In 1968 USP headquarters moved from New York City to Rockville, Maryland. In1970 USP created the position of Executive Director, filled by William M. Heller, Ph.D.
In 1975 USP acquires Drug Standards Laboratory from the American Pharmacists Association(APhA), and signed an agreement with the American Medical Association(AMA) to combine the information in AMA's Drug Evaluations Database with the USP's DI database.(USP is no longer engaging in the DI database. This kind of information is provided by National Library of Medicine and by several private companies.)
USP initiated establishing standards for botanical dietary supplements in 1995, and launched an Internet-accessible medication errors reporting program in 1998. (USP is no longer engaging in the medication errors reporting program. Currently USP, ISMP:Institute of Safe Medication Practice, manufacturers and Med Watch report medication error information to FDA.)
Also in 1998 the new Reference Standards Center opened.
In 2006 the Food Chemical Codex was acquired by USP from the Institute of Medicine.
On the other hand, in 1963 United States Adopted Names Council (USAN Council) was formed by the representatives from AMA, APhA, FDA and USP. It is establishing drug nomenclature.
In 2000 Dr. Roger L. Williams, M.D. becomes USP's CEO.
Looking back on the history, USP has a responsibility on national-wide standards setting according to the law from the first, and deep relations with AMA, APhA and FDA upon its activities. USP sets the public standards which provides the criteria of judgment for manufacturing, retailing, compounding, testing and enforcement of pharmaceuticals and related products, and takes an important role to ensure the quality, safety, and efficacy of medicines for public health in USA.
2. Current activities
USP Mission is "to improve the health of people around the world through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods".
USP is a nonprofit public health organization with more than 500 staff members, whose work for revising compendium and establishing new monograph is accomplished by a body of more than 1000 volunteer experts.
Besides the headquarters in Rockville, USP has local offices in Basel(Switzerland), Hyderabad(India), Shanghai(China) and San Paulo(Brazil) for verification and education in the sites.
USP Headquarters have several staff member teams for Monograph, General Chapter, compounding, Nomenclature, safety and labeling, Reference standards, Statistics, Toxicology. Both Monograph and General Chapter teams have projects with Small molecules(chemicals), Biologics & biotechnology, Excipients, Dietary supplements and Food Ingredients.
Current USP activities are;
- Create and revise documentary standards and publish compendials
- United States Pharmacopeia(USP), National Formulary(NF)
- Standards for dietary supplements and ingredients, Food Chemical Codex
- Develop and maintain the reference materials
- Allied compendial programs
- US Pharmacist Pharmacopeia
- USAN
- Education program
- Verification services
- Technical assistance for developing countries
USP is monitoring advances in science and technology and other changes in the healthcare environment, operating internationally to the public health in the world, building and expanding relationship with domestic and international organizations and other stakeholders, and engaging in programs promoting the use of public standards to improve the quality, safety and benefit of medicines and foods. USP is indicating the importance and relevance of the independent standards-setting compendial organization in today's global marketplace for world-wide public health.
3. Next 5-year activities plan of USP
USP's activities are based on the resolutions, constitution and bylaws, council of experts, and officers and trustees. These are determined by the USP Convention's membership Meeting which is held once every five years to bring together USP Convention volunteer members to discuss them. This meeting is held in April 21-24, 2010 and determines the USP activities from July 2010 to June 2015.
After election of new members of Council of Experts, Expert Committee members are organized and succeed to the previous discussion on standards setting.
Current strategic plan is available on the USP web-site. In this strategy, with the scientific decisions by the volunteer scientists and healthcare professionals in US, USP is aiming for expansion and enhancement of compendial activities, strengthening USP's allied compendial programs, engaging in other programs to fulfill the public health needs, and in national and international operation, to help improve the quality, safety and benefit of medicines and foods worldwide. USP envisions a world to improve the health of people around the world.
4. Expert Committee and Ad Hoc Advisory Panel of USP
According to the rules and procedures determined by the Council of Experts, USP organizes the Expert Committees in each project. Expert Committee members are composed of professors and researchers in medical, pharmacological, scientific field from universities and companies in US. Some committees have experts coming from research institutes of China and India.
Meeting is held in the USP's meeting room. Some committee members participate in the meeting by telephone equipments, but they have almost no difficulty in discussion because the meeting documents have already been sent to them.
Expert Committee members shall be required to adhere to the USP Code of Ethics and related Policies, shall serve USP as individual experts, do not serve any outside interest or private gain for himself/herself. Each member shall sign a confidentiality agreement with USP to maintain the confidentiality of all non-public information in the committee.
The Expert Committee may invite a guest to share a particular expertise and point of view on the agenda, may permit observers who had notified at least 5 days in advance of the meeting. The chairperson shall ask the invited guest and the observer to excuse himself/herself during a confidential discussion.
The Expert Committee mostly designate a FDA Liaison person (Government Liaison) coming from the corresponding section of FDA on the required activities of the Committee. Other FDA staff members sometimes make presentation and participate in the discussion on the agenda items.
The Expert Committee meeting is practically managed and supported by the responsible USP staff members for the committee in concert with the chairperson.
Other USP staff members participate in the specific section of the meeting to make their presentation and to observe the discussion. Sometimes chairperson asks the USP staff members their comment or opinion.
The Expert Committees are responsible for developing and revising public standards, and important decision for final text of compendial publication is voted on and approved by the Expert Committee.
In addition, Ad Hoc Advisory Panel may be formed by the chairperson of the Council of Experts to perform assigned specific task for a particular Expert Committees.
5. Recall of the USP 33 - NF 28
USP recalled USP 33 - NF 28 because of errors that occurred when monograph were redesigned into a new format. USP releases reissue and first supplement in April in advance to their official date of October 1,2010. These recall and reissue are measures in order to avoid from mistaking in the process of manufacturing and compounding of medicines. The electric version (web and CD) and the print version will be available. Sending to the purchased customer in US is first, followed by shipment to other countries.
6. FDA Advisory Committee
FDA Advisory Committees are established in consistent with the Federal Advisory Committee Act, and their procedures and rules are set forth in general terms in the agency's regulations in 21 CFR Part 14: Public Hearing before a Public Advisory Committee. Openness of the agencies' meetings and public notifications in the Federal Register are maintained in accordance with the Government Sunshine Act established in 1976. Also FDA provides the guidance document for management of the Conflict of Interest and information transparency.
Each Center of FDA has specific procedure on the subject of different FDA-regulated product with different risk and decides to bring an individual matter to the advisory committee. FDA provided the draft guidance document for public and FDA staff on convening advisory committee meetings in August 2008. This draft guidance sets forth FDA's current thinking on factors each Center considers in deciding whether to bring a matter to an advisory committee. The factors are;
1) Issue of such significant public interest
2) Issue so controversial
3) A specific type of expertise is needed
FDA Advisory Committee provides independent expert advice to the Agency on a range of complex scientific, technical, and policy issues. And advisory committee meeting also provides opportunities for a public hearing on important matters. Although advisory comittees provide recommendations to FDA, FDA makes the final decisions. To enhance the transparency of the activities, FDA seeks input from Advisory Committee on a broad scope of complex issues which are in the public interest.
FDA is managing about 30 Advisory Committees (about 20 for drugs, about10 for medical devices, and others, for example scientific committee, risk communication committee etc).
Operation procedure of the Committee meeting is different to each meeting agenda. One of the examples of the meeting about Committee's advises to FDA on approval of new drug or medical device application, is expedited like this:
- 90-minutes Sponsor presentation and Questions
- 90-minutes FDA presentation and Questions
- Open Public Hearing
- Deliberations
- FDA Questions to the Committee
- Committee discussion / Vote
Meeting is generally scheduled for one day meeting from 8 am to around 5 pm.
After the announcement of the Advisory Committee interested persons may make submission to FDA to present views or information on issues pending before the committee. The meeting is open in principle, and usually any person can observe it without registration at the backyard observer area (about 200 seats prepared). Observers can obtain the black and white copies of presentation slides, but they cannot approach the committee member table in the shape of U across the rope.
Discussion is recorded on tape and video. Minutes and transcript is available on the web-site later. Electric voting is done simultaneously and its result is displayed on the screen. Each committee member makes a comment on his/her decision.
Sponsor and FDA prepare several additional slides in advance for Committee member's questions besides the 90-minutes presentation. They also prepare an extra slides and explanation during the 1 hour lunch time, and make short presentation in the afternoon discussion.
The schedule is strictly observed and each presentation ends punctually. Sponsor, FDA and Committee member speak carefully and explain thoroughly. One day meeting seems to provide sufficient discussion in the Committee.