Anatomy of a Drug Recall

by Winton B. Rankin

' T

he drug industry, the pharmaceuti~ cal profession , and the Food and Drug Administration share the common goal of achieving excellence in drug production. However, there are instances where substandard drugs find their way into the market place in spite of the elaborate preventive measures that ar~ being taken. When these unfortunate incidents occur, it is both government's and industry's responsibility to see that the .products are removed from the market as soon as possible. This may be done through industry's voluntary effort-by recallor it may require the use of court action. Recalls may be cataloged into three groups~

the recall that is caused by problems of pharmaceutical elegance only -crooked labels on the bottle for example. ~

the recall that represents a more serious problem but is wholly voluntary on the part of the firm. ~ the FDA-initiated recall where the firm is requested by the commissioner to remove a product from distribution.

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why drug recalls There are many different reasons why faulty drugs get into the marketplace. Defective drugs can occur because 'Of breakdowns in drug production or distribution. This is a large area 'Of concern and covers many diverse reasons. However, an analysis of fiscal year 1966 drug recalls indicates that three-fourths of them were f'Or reas'Ons which oould be related to failures by manufacturers to observe the minimum requirements of the current Good Manufacturing Practice Regulations. They included drugs which were subpotent or , overpotent, cross-oontaminated with other drugs, nonsterile, mislabeled or deficient in other ways such as failure t'O meet all requirements of the official compendiums. mechanism. o·f drug recalls As soon as FDA learns that a product is seriously misbranded or adulterated and after it has collected sufficient facts to determine that there is a potential for harm to oonsumers, the machinery is immediately set in motion to get the product off the market.

Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION

While the recall is being oonducted, we continue t'O amass additional facts about it through factory inspections, field investigations and laboratory examination of samples. We attempt to determine as soon as possible the amount IQf the drug on the market, the lot number involved, complaints of adverse reactions, the periods of distribution and the extent and area of distributi'On. The depth to which an offending product is recalled depends primarily on the degree 'Of the health hazard. This decision is reached on a case-bycase baSIS and involves a careful review and evaluation of the available data by FDA's Bureau of Medicine. Some recalls extend all the way to the pharmacist, the doctor, hospital and even the home, while other recalls will not go below the wholesale or branch warehouse level. Of course, it is our policy when we encounter a drug which is a health hazard to advise the manufacturer, or other responsible party, of our findings immediately and ask that the product be recalled. If the finn can recall the drug and wishes to do so, we will assist in getting the recall under way

promptly. Conversely, if the firm cannot or will not recall the product, we will proceed promptly with seizures of available lots and, if necessary, with publicity. We also advise state regulatory officials and, where their assistance is needed to get a hazardous product off the market promptly, we request it. When it is necessary to alert the public to a ~rug recall at the community pharmacy or consumer level, the firm involved is so advised and invited to issue a press release. FDA will issue a release if the firm chooses not to do so or if an agency announcement is necessary to alert the public to a critical health hazard. And I want to e~phasize that when we do approach a firm concerning a recall or a press release, management is invited to submit any data it has which bears on the matter. FD A recognizes that a recall is to be used only under the most serious situations. Thus, only the commis-

sioner of food arid drugs, the depti~y commissioner or the associate ~ommis­ sioner for compliarice may authorize aIi FDA request £or recall. Before one of these officials acts, . he draws upon the entire expert.ise and .counsel of the scientific and administrative resources of FDA. increase of drug recalls

There has been a marked upward trend in drug recalls .in recent years. For instance, drug recalls increased from 340 in the fiscal year ending June 30, 1965 to 446 in fiscaJ year 1966. Iri fiscal year 1967, the figUre increased to 622. The large number of recalls must not lull us into .accepting them as a normal part of the mar.keting of drugs. The. recall indicates that something abnormal has occurred. All of us must strive to eliminate the basic problems. While part of the 0\)

o All figures exclude veterinary vitamins and drugs, diagnostic agents and medicated feeds.

increase may be ~nd p~~bably is due to better reporting, the trend ~annot readily be explained. away on this basis . . There is a real problem here that must be corrected. national center for dr~g ~naiysis

The number of recalls is not the only indicator that can be used to measure the quality of the American drug .supply. Another in.-dicator that is presently being developed is , the program recently launched at FDA's N aUonal Center for Dx:ug Analysis in St: Louis, Missouri, to monitor the drug supply of our nation on a continuing basis. . . . In essence this is the public's. drug control laboratory which; . through the use of aut!omated ~quipment and the newest as~ay technics, will enable FDA to test over 150,000 lots of marketed drugs annually. ~amples for this monitoring are collected on sfatistical basis not only fvom community pharmacies but from hospital pharmacies

a

FDA proposed model letter, notification card and envelope for recalls.

JpHN nOt LABO ' RATORlts

Somewh

JOHN

DOE LABORATORIES

er~ US

' • . A. 12345

Somewhere, U. S. A. 12345

A. B. C. Pharmacy Anywhere, U. S. A.

URGENT: DRUG RECALL

PLEASE FI LL OUT AND RETURN

We do not have any stock of List 1234 , Cyanocobalamin injection Lot No. 4321 on hand. c=J We are returning_ _ _bottles of List 1234, Lot No. 4321 NAME:_ _ _ _ _ _ _ _ _ _ _ _ _ __ ADD RES S: _ _ _ _ _ _ _ _ _ _ _ _ __ CITY_ _ _ _ _ _ STATE_ _ _ZI P CODE _ _ •... ::::::,.,===_===_z C

i First Class

n Permit No.2:: ~

III dlille. IIlI n lill

r.

t===~~~:~~_c:_~

JOHN DOE LABORATORIES

Somewhere , U. S. A. 12345 Henry Doe

Director, Quality Control

Vol. NS7, No. 11, November 1967

571

On the basis that the symptomsdrug recalls-will be with us for some time to come, APhA has been the catalyst in stimulating action by the National Drug Trade Conference to form a study group on drug recalls. The objectives of this study group are~

Winton B. Rankin, deputy commissioner of the Food and Drug Administration, joined FDA in 1939 as a seafood inspector after community pharmacy practice in North Carolina. He has served in FDA as a food and drug inspector, assistant director in the division of field operations and assistant to the commissioner in various capacities. He was appointed to his present position in 1966. An honorary member of APhA, Rankin holds degrees in education (BS), pharmacy (BS) and chemistry (MS). He is a member of AAAS, Association of Analytical Chemists and American Management Association. In 1965, he was the recipient of an honorary doctor of science degree from Ferris State College for outstanding contributions to pharmacy.

and other sources. The intelligence provided by the results of this program will be the best objective measure to date of the overall quality of the nation's drug supply. It undoubtedly will stimulate improvements in the analytical testing performed in the quality control laboratories of drug manufacturers. But this FDA program is nGt the only stimulus. We welcome the efforts by several groups including the American Pharmaceutical AssGciation's Academy of Pharmaceutical Sciences to improve drug testing and to understand better the mechanics of the action of drugs. Improved testing of drugs before marketing will reduce drug recalls. treating the symptoms

Neither industry nor FDA can ignore the rising trend of drug recalls, especially in the face of increasing public demand for better drugs. Recalls, however, must be viewed as symptoms 'Of an ailment. Symptomatic therapy is necessary but therapy must be applied also to the ailment to remove the underlying cause. 572

1. to. review existing pro.cedures in getting drug recall info.rmatio.n from manufacturers to. whelesalers, cern· munity pharmacies, ho.spital pharmaciesand physicians 2. to. stimulate all these gro.ups to. co.o.perate to. get recalled drugs o.ff the market quickly ~nd effectively 3. to. co.nsiderthe establishment o.f a natio.nal clearing ho.use fo.r drug recall information which will provide a framework on which industry might build its own program for more effec-. tive handling and mo.nito.ring ef drug recalls

An endeavor such as NDTC's study group is an excellent example of cooperation where all parties recognize both the moral and legal responsibility of working together when the interest of the public's health is involved. One excellent result of this cooperative program to date has been the con.; structive comments ,F DA has received on the basis of which it improved its weekly drug recall list. These improvements have made the informatiGn more responsive to the needs of the drug industry and health professions thi"ough more complete product identific~tion and product labeling, the quantity of each recalled lot distributed with bracketed dates of distribution, date or initiation of recalls and separation of drugs from other recalls. F or a recall to be effective there must be good communications from the manufacturer to corisignees who have received the recalled drug. Prior to 1965 FDA found that many recall letters were less than forthright and had no earmarks of urgency. Therefore, in 1965 FDA proposed the use of an initial mude! recall letter and a distinctive envelope (see examples on page 571). Recall letters have improved. Yet . there is still need for a strong educational campaign to be sur~ that consignees respond promptly to such letters. NDTC and other groups can be of great help here. treating the ailment

One of the most significant strides iri the intensive effort to reduce drug recalls has been the series of joint FDAindustry workshops on current Good Manufacturing Practice Regulations conducted over the past several years. This w1orkshop concept was pioneered in August 1965 by the Pharmaceutical Manufacturers Association and the University of Wisconsin school of pharmacy when they jointly sponsored

Journal of the AMERICAN PHARMACEUTICAL ASSOOIATION

a seminar on good manufacturi~g prac. j tices attended by representatives of about 100 drug producing establish. ments. At this seminar and its sue· ceeding one in 1966 at Hershey, Penn. sylvania, great stress was placed on the need to train and motivate per· sonnel toward the goal of error elimi. nation. The prGceedings 'Of the second seminar held in 1966 have since become one of the m'Ost important reference books on Good Manufacturing Practices available today. FDA's drug industry educati'Onal' program is expanding to reach the· regulated industries and health pro~ fessions at the grass roots level. For instance FDA district offices, in cooperation with the Bureau of Education and Voluntary Compliance, have held 22 district workshops and seminars in. volving 912 ,firms this past year on the subject of good manufacturjng practices. Five national conferences· and symposiums also have been held in specific problem areas such as particulate matter in large volume parenteral solutions and sterile disposable medical devices. FDA has noted that stuciies of good manufacturing practices are becoming a standard part of the curriculum in courses in manufacturing pharmacy. The attention which manufacturers must nGW give to recruiting highly trained individuals for their quality control departments will unquestionably place increased demands upon the pharmaceutical skills of the nation. We are extremely proud 'Of the steps our schools of pharmacy are takIng to meet these needs. self·,ins'p ection

Many ,firms are including an impor-. tant new dimensi'On in their quality control procedures-the technic of selfinspection. This idea is not a new ·one but the concept is spreading among forward-thinking drug firms. Self-inspection is a procedure where one or m'Ore ·specially trained quality control or other key personnel are assigned to inspect routinely all 'Operations to check conformance with the GMP Regulations. Under such a plan a fin:n actually carries out its own "in-plant" inspections to supplement fhose ·of FDA. There is .no doubt that suc~ a program is worthwhile. summ,a ry

While drug recalls will probably be with us fGr some time to come, steps are being taken to reduce the number: With help from many quarters we have a program 'Of seeking out and cataloging the exact causes of drug recalls. This cumulative information will then permit us and the drug industry to establish better preventive measures to eliminate the problems. •