Maintaining CGMP Current Good Manufacturing Practices
May 01, 1998
by Teresa Acklin
Current Good Manufacturing Practices require various guidelines to ensure safety and purity in the feed industry.
By Bill Harriman
Current Good Manufacturing Practices (CGMPs) are a concept that evolved in the United States many years ago. The first evidence of CGMPs in the U.S. appears in the human drugs and devices section of the Food, Drug & Cosmetic Act enacted in 1938.
The law says: A (human) drug shall be deemed to be adulterated...if it is a drug and the methods used in, or the facilities or controls used for it, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.
This language obviously implies there is some standard practice by the legitimate industry whatever the practice. This certainly can and does apply to the feed industry.
The U.S. first proposed CGMPs as a regulatory tool for human foods in 1967 and adopted them in 1969. In 1968, a law was passed regulating animal drugs in the U.S. This law adopted CGMP language presented earlier for animal drugs. The U.S. adopted CGMPs for medicated feeds shortly thereafter.
The basic concept of CGMPs is simple. The “C,” which stands for “Current,” is an extremely important principle in the process that recognizes that GMPs are not stagnant, but rather dynamic, and thus subject to a change in any standard practice. Examples include new types of equipment or new standards for microbiological control. Ingredient receiving, process controls, cleaning procedures and loading procedures change with time; thus, current good manufacturing practices are those practices in use by the legitimate industry at any point in time.
Since feed manufacturers make food for animals that are ultimately consumed by humans, we are essentially in the “food business” and should rightly be governed by the same precepts of the food industry. However, the standards of sanitation and manufacturing control would differ for human and animal food. Therefore, from the question of what is a legitimate manufacturing process for the feed industry arose the idea of applying CGMPs from drugs and foods to feeds. It would make little sense to apply human food and drug CGMPs to feed manufacturing because such procedures would be very costly and result in little commensurate benefit beyond CGMPs specific use for the feed industry.
Similarly, the U.S. has sanitation CGMPs for food, which do not apply to feeds, as well as distinct CGMPs for medicated feed, which are specific for feed manufacturing.
The CGMP concept is a simple one. The affected industry, in this case the feed industry, decides what are the commonalties practiced by every industry member to ensure that feed manufactured with animal drugs is safe, has the identity and strength, and meets the quality and purity characteristics that it purports or is represented to possess. That is, animal drugs used in feed should be carefully stocked, checked, added to feed and mixed, labeled, stored and distributed along a given set of guidelines that all the legitimate industry agrees are necessary to ensure a safe feed, and therefore, safe food.
Developing Industry Standards
Trade associations are an important tool in developing CGMPs in cooperation with government oversight agencies. Trade associations allow each industry representative to meet with other industry officials and develop common approaches to an issue. These trade associations allow manufacturing firms to develop industry approaches that could not be done individually. In other words, to work for the common good and do collectively what cannot be done individually.
Obviously, no one company or firm can develop an industry standard or CGMP. The industry is a dynamic, growing process with new technologies and new ingredients and as such, developing CGMPs must be a continuing group effort.
CGMPs are the bedrock of any food manufacturer, whether recognized by that acronym or not. All food industry CGMPs have common provisions but may differ by degree, specificity or actual topic.
Frequently, the actual written CGMP may be quite broad to allow for a general interpretation as to achieve the endpoint of producing a safe feed. This is especially important for regulatory programs, where a CGMP is developed by an industry/government working group, but is implemented within a surveillance/inspection program. The inspector or investigator, whether government or private, usually is not present at the development phase of the CGMP program, but is expected to read and interpret a standard and determine compliance with that standard. This may result in an unlevel field of commerce because of varying interpretations by investigators of a standard developed by industry leaders.
So, why should an industry support CGMPs? First, they are and should be current practices; second, they attempt to and often do level the field of commerce and assure an industry that manufacturers are playing by the same rules; and third, CGMPs provide some standard that is important in upholding consumer confidence in the production of meat, milk and eggs. The second issue of leveling the field of commerce is important and is predicated on some kind of industry or government surveillance program.
The first CGMP topic is personnel. It would appear obvious that a firm would have trained adequate personnel to manufacture feed, but how workers are trained, who trains them and what they need to know are the questions that should be asked.
The level of specificity of the operation, i.e., drugs, food or feed, determines the depth or degree of the training requirement. The key to success in quality assurance in our organization is the mill manager and his quality control supervisor. We emphasize that quality is everybody's job.
Buildings and facilities should be adequate for the intended purpose. They should be well-drained, free of litter and waste, reasonably clean and orderly, of suitable size, adequately lit, and so on. This leaves considerable latitude about what constitutes “reasonably clean.” One investigator's clean may not be another person's clean.
The principal factor is what impact does the building and its condition or design have on the outcome of producing a safe feed. This question should be asked time and time again with every topic.
Equipment should be of adequate design and size to perform its intended function. Most importantly, all equipment should be capable of producing a medicated feed of intended potency, safety and purity.
Scales and metering devices should be accurate and precise. You can't weigh an animal drug in grams on a scale with one-half kilogram gradations. Even though this scale may be very accurate, it is not precise enough for such measurements. Also, equipment design should facilitate clean-out.
Product Quality Control
After the consideration of the facilities and personnel, the area of product quality control is the next important area and comprises several topics, the first of which is components.
In a medicated feed manufacturing facility, the most important component is the animal drug. In the U.S., F.D.A. approvals are required before purchasing or mixing any drug into animal feed, further mixing medicated animal feed or even repackaging a medicated feed.
Animal drug approvals are very specific. Animal and human health protection demands use of animal drugs in feeds only in accordance with their respective F.D.A. approval.
The mixing facility must have a feedmill license in order to purchase Category II, Type A drug sources, the so-called “human risk” drug sources. Medicated feed mixers who choose not to use human risk drug sources are subject to a separate, more relaxed set of CGMP regulations. The categories and drug sources are:
Category I requires no withdrawal;
Category II requires a withdrawal;
Type A -medicated articles;
Type B medicated concentrate feeds;
Type C complete ready-to-feed or free choice.
A 1996 U.S. law creates a new category of drugs called veterinary feed directive (VFD) drugs. The VFD differs from a prescription in that the VFD only authorizes the use of the drug in accordance with its F.D.A. approval.
Only feed mixing facilities that hold a valid feedmill license can mix drugs restricted to a VFD in animal feed. A drug restricted to a VFD can only be sold to a feeder who holds a valid VFD.
Similarly, consideration can be given to quality factors, such as contaminants, degradation and nutrient level, in other feed ingredients. It is the plant's responsibility to inspect each and every inbound shipment for conformance to established physical specifications, preferably prior to the start of the unloading.
This inspection is our first defense in preventing inferior ingredients from entering our plants and is the responsibility of the plant quality control supervisor. We impress on our people that quality control starts before the ingredient is unloaded.
We maintain an ingredient analysis schedule, which is a program for auditing each ingredient supplier to determine that specifications are being met. A summary and specifications sheet is kept for each supplier.
This analysis schedule is the base document from which the appropriate assays are assigned to ingredients. This schedule indicates how often an analysis will be required on the basis of the number of shipments received.
For example, it may be every shipment or every fourth shipment. We require a certificate of analysis on every shipment of fat certifying that it is free of pesticide residues and polychlorinated biphinols. The purpose of the pesticide residue prevention program is to assure that all poultry intended for slaughter is in compliance with and free from pesticide residue tolerances.
Receipt, storage and inventory of animal drugs is an important control point in a feedmill. Drug packages should be inspected, identified, stored and handled in a way such that the integrity, purity and quality of the drug lot is preserved.
Daily drug inventories are essential for control of components. Reconciling inventories and handling of any discrepancies in components should be a mandatory function.
In our organization, we accomplish this with a daily drug inventory report. The purpose of this record is to verify that each drug was used correctly. If the balance on hand compared to the previous day's activity is not within an acceptable tolerance, an immediate investigation is made.
The periodic assay of medicated feed provides a laboratory control that may be necessary to quality control. However, it should not be the only control as interfering substances and poor analytical performance may result in false results. Reliance should be placed more on the inventory and production records to best ensure quality assurance of products produced.
Each U.S. feed manufacturer holding a federal facility medicated feed license is required to assay each Category II, Type A drug containing feed three times a year and report any confirmed, out-of-limits assays to the F.D.A. We do this with a feed analysis summary.
This record is maintained for each feed sample tested by the laboratory on each type of feed produced on a regular basis. When the results from the weekly laboratory reports are received, they are entered onto this form.
This type of record allows for quick discovery of trends that may develop and for follow-up corrective action before the problem gets out of hand. Section 225.58(d) of the GMPs states that “…where the assay results indicate that the medicated feed is not within permissible assay limits an investigation and corrective action shall be implemented and an original copy of the record of such action maintained on the premises.”
The record to be filled out and maintained for investigative and corrective actions on out-of-tolerance assays is called the Drug Control Report. When the retained sample comes back, out-of-tolerance samples must be submitted from the next three production batches of this same feed for analysis and must be recorded in the table provided on the Drug Control Report.
Modern commercial feedmills use a number of approved animal drugs and frequently manufacture feeds for a variety of species. Special attention should, therefore, be paid to equipment clean-out procedures.
Adequate procedures are essential to maintain proper drug potency and avoid unsafe carryover and contamination of feeds with drugs. Flushing of equipment and sequencing of feeds are the two most common methods of equipment clean-out in the U.S.
Flushing may be by sweeping, vacuuming or washing, whereas sequencing feeds is more complicated. We maintain a flushing/sequencing validation form that periodically assays residue results to ensure that our flushing program is adequate.
We group feeds and schedule all medicated feeds having the same drug in sequence starting with the highest level. We have a list of approximately 25 drugs that should never precede the production of a feed designed to be fed to animals prior to slaughter. A flush/chaser must be used if sequencing is not possible.
After developing guidelines to control the manufacturing process, adequate labeling and packaging are necessary to prevent mix-up and assure proper use of the medicated feed products. Label control is a necessity to maintain adequate control of packaging.
Records and reports are important tools in documenting what occurs during manufacturing and are good business practices as well.
A master record file contains the formula, yield, procedures, assay requirements and any labeling requirements of batch or production runs. The files should be prepared, checked and verified by qualified personnel.
Production records should be the complete record of the manufacturing process developed from using the master record file. These can be stored in file cabinets, a central location or in computer files. Each batch or production lot should be coded to facilitate the identification and tracing of distributed lots of feed. Lots must be coded, then distribution records must be maintained to ensure the ability to trace any distributed lot.
A common CGMP topic in the U S. is the complaint file. Firms need to be alert to products that fail to achieve their intended effect, especially with respect to any medication in the feed. Complaint files may also be important in defending against liability claims against the feedmill.
A complaint file typically contains identification information and should include the lot number of the feed distributed. This is where lot coding is important.
We believe a comprehensive quality control program is vital to the success of our poultry and feed business. The quality of our broiler feed and commercially sold feed is directly related to the results at our patron's farms.
These topics: personnel, buildings, equipment, work areas, components, laboratory controls, equipment clean-out, master record files and production records, distribution records and complaint files make up the CGMPs basics. These are the same topics used in CGMPs for the human/animal drugs, foods and medical devices. Only the degree of specificity and the type of industry makes each set different or more expanded.
CGMPs are time-tested and offer a real way to assure our customers and the consumer, as well as government regulators, that our products and processes are “in control” and our products are manufactured to ensure safety, identity, strength, purity and quality.
In the U.S., products may be considered adulterated and in violation of federal and state law if the products are not manufactured in compliance with CGMPs. This says that the products themselves do not have to be adulterated, per se. In other words, the products become adulterated if they are not manufactured by a company considered to be in control of its quality of manufacturing processes or products, that is, in conformance with CGMPs.
Such a finding is serious and renders all products produced in such a plant to be unusable or unavailable for sale. Frequently, the plant may not begin manufacturing after such a finding unless the CGMPs violations are corrected and the plant has been re-inspected and passed the inspection.
CGMPs are nothing more than good business practices that should be practiced by all feed manufacturers in every country. But the CGMPs should be specific to a country or region as trade issues, cultural differences and other factors can influence the development and final implementation of CGMPs.
This article is based on a presentation by Bill Harriman for the 3rd East/West Industry Conference in Prague, the Czech Republic, in June 1997, which was sponsored by Victam International and the International Feed Industry Federation. Mr. Harriman is director of feed manufacturing services within the poultry group of Gold Kist Inc., U.S. He is currently chairman of the American Feed Industry Association.CGMPs: an outline
H.A.C.C.P. and quality control
|The following points cover the entire spectrum of Current Good Manufacturing Practices for food, drugs and feeds as set out by U.S. law. Although they may seem quite simple, the development of the details is frequently time consuming.|
| ||Current good manufacturing|
| ||Personnel |
|||Construction and maintenance|
|||Product quality control|
| ||Laboratory controls|
|Equipment clean-out ||procedures|
|||Packaging and Labeling|
|||Records and reports|
|Master record file and ||production|
Although buildings and equipment are general areas of concern, work areas are important and should be adequate for their function and free from non-ingredients. Good housekeeping is a must. The space program brought a new quality program into being called the Hazard Analysis of Critical Control Points.
|The seven point program involving a H.A.C.C.P. plan is:|
|1.||Hazard analysis. Identify the hazards inherent in specific manufacturing process.|
|2.||Identify the critical control points. This includes points in the process of manufacturing and delivering feed, points in the process where possible contamination can be avoided and product sterilizing points.|
|3.||Establish critical limits. Preventive measures associated with each identified critical control point.|
|4.||Establish procedures to monitor critical control points. Once critical limits have been set, it becomes obvious that these need to be monitored in a timely manner. Examples are the temperature of the pellet, ingredient receiving, the sampling plan, etc.|
|5.||Establish the corrective action to be taken when monitoring shows that a critical limit has been exceeded|
|6.||Establish effective record keeping systems that document the H.A.C.C.P. system.|
|7.||Establish procedures to verify that the H.A.C.C.P. system is working. Verification of the H.A.C.C.P. plan is simply a review of the records on a quarterly basis by the feedmill manager in conjunction with the director of quality control. The H.A.C.C.P. type plan for feedmills was recommended by the American Feed Industry Association Microbiological Task Force after earlier work by the A.F.I.A. Salmonella Task Force. The A.F.I.A. top priority remains food safety.|