Inspections and Final Report Audits for ... - ACS Publications

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Chapter

12

Inspections and Final Report Audits for Environmental Studies Patricia D. Royal Battelle Ocean Sciences, 397 Washington Street, Duxbury, MA 02332 Enactment of the Good Laboratory Practices (GLP) regulation by the U.S. government was a direct result of an investigation conducted in 1975 by the U.S. Food and Drug Administration (FDA). That investigation evaluated the integrity of health assessment studies used to support registration of food additives, drugs and cosmetics under the Food, Drug and Cosmetic Act (FDCA). The conclusion of this investigation revealed flawed study conduct, inaccurate reporting, and inadequate data integrity. The FDA then implemented regulations affecting study conduct and data collection and retention. These regulations govern reporting requirements for health assessment studies used to support registration under FDCA and are commonly referred to as the GLPs (1). Shortly thereafter, the U.S. Environmental Protection Agency (EPA) developed similar requirements under the Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) and the Toxic Substances Control Act (TSCA) (2) (3). Together, these three regulations control the conduct and reporting requirements for a l l industrial safety assessment studies used to support registration of chemicals, pesticides, food additives, and drugs by EPA and FDA. Although environmental and chemical fate studies were included in the original TSCA/GLP, they were not specifically identified in FIFRA/GLPs. This inconsistency slowed the development and implementation of compliance programs by EPA to evaluate ecotox and the analytical chemistry associated with environmental studies. EPA is now proposing to fill that gap by redefining the scope of existing FIFRA/GLPs to include environmental and chemical fate studies. Impact and Implementation Expanding the scope of FIFRA/GLP to include environmental and chemical fate studies will take time. It will mean that studies described by EPA Hazard Evaluation Division, Office of Pesticide and Toxic Substances, for Environmental Fate and Residue Chemistry must meet the requirements outlined in the FIFRA/GLPs, and that 0097-6156/88/0369-0075$06.00/0 © 1988 American Chemical Society Garner and Barge; Good Laboratory Practices ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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l a b o r a t o r i e s and f i e l d o p e r a t i o n s c o n d u c t i n g t h e s e s t u d i e s w i l l be m o n i t o r e d by the EPA O f f i c e o f Compliance M o n i t o r i n g . I t i s always v a l u a b l e when implementing a new program t o a s s e s s the impact of the program on the o p e r a t i o n s and t h e p e o p l e i n v o l v e d . One o f the c o n c e r n s v o i c e d by s c i e n t i s t s has been t h a t GLPs i n t e r f e r e w i t h t h e advancement o f s c i e n c e . T h i s i s e s p e c i a l l y t r u e i n f i e l d t e s t i n g programs and i n a n a l y t i c a l c h e m i s t r y l a b o r a t o r i e s where e x p e r i m e n t a l p r o c e d u r a l development o f t e n t a k e s p l a c e . Implementation o f the GLPs i n t o t h e s e programs w i l l not d i c t a t e s c i e n t i f i c p r o c e d u r e , but w i l l r e q u i r e p u t t i n g s c i e n t i f i c p r o c e d u r e i n w r i t i n g , and w i l l r e q u i r e documentation to t r a c e the p r o g r e s s o f the s t u d y . Implementation at the t e s t i n g s i t e w i l l mean d e v e l o p i n g SOPs for a p p l i c a t i o n of t e s t substance, randomization, l o c a t i o n , i d e n t i f i c a t i o n , and c o l l e c t i o n o f samples, and e s t a b l i s h i n g sample c u s t o d y p r o c e d u r e s t o e n s u r e sample i n t e g r i t y w h i l e i n t r a n s p o r t t o the l a b o r a t o r y . In the l a b o r a t o r y , i m p l e m e n t a t i o n w i l l mean t h a t the equipment and the f a c i l i t y must be o f adequate s i z e t o m a i n t a i n the i d e n t i t y , s t o r e , and a n a l y z e a v a r i e t y o f samples. A d d i t i o n a l a r c h i v a l space w i l l be needed t o p r o v i d e s t o r a g e f o r a n a l y t i c a l samples, s o i l and p l a n t specimens. There must be p r o c e d u r e s f o r documentation o f sample i d e n t i f i c a t i o n and r e c e i p t from the f i e l d t o v e r i f y sample c u s t o d y p r o c e d u r e s , p r o p e r sample s t o r a g e and waste d i s p o s a l . The l a b o r a t o r y must have v a l i d a t e d p r o c e d u r e s f o r the t y p e of c h e m i c a l a n a l y s i s being conducted. L i k e w i s e , t h e r e must be documentation o f the t r a i n i n g and a n a l y t i c a l p r o f i c i e n c y o f the s t a f f . Standard O p e r a t i n g P r o c e d u r e s (SOPs) must be w r i t t e n t o d e s c r i b e the a n a l y t i c a l methods used, and t h e maintenance and c a l i b r a t i o n o f equipment. P r o t o c o l s o r work p l a n s must be e s t a b l i s h e d t o s p e c i f y t h e o b j e c t i v e o f the s t u d y , p e r s o n n e l i n v o l v e d , equipment, and methods, i n c l u d i n g c r i t e r i a f o r a c c e p t i n g o r r e j e c t i n g d a t a and the f r e q u e n c y f o r r u n n i n g s t a n d a r d s , s p i k e s , and b l a n k s , commonly known as Q u a l i t y C o n t r o l (QC) s t a n d a r d s . A p p l i c a b l e methods f o r d e v e l o p i n g t h e s e programs can be found i n 40 CFR, 136, and Q u a l i t y C o n t r o l i n A n a l y t i c a l C h e m i s t r y , by Kateman e t a l . ( 4 ) ( 5 ) . The term Q u a l i t y A s s u r a n c e i s o f t e n c o n f u s e d w i t h Q u a l i t y Control. Q u a l i t y A s s u r a n c e i s a program e s t a b l i s h e d t o m o n i t o r study conduct and r e p o r t i n g t o ensure t h a t they meet b o t h e x t e r n a l and i n t e r n a l s t a n d a r d s . I n t h i s r e g a r d , i t i s a management t o o l . Q u a l i t y C o n t r o l (QC), on the o t h e r hand, i s the c r i t e r i o n o r i n t e r n a l n u m e r i c a l s t a n d a r d on which the a c c e p t a b i l i t y o f d a t a i s judged. By i d e n t i f y i n g some o f the unique needs f o r v e r i f y i n g conformance t o s t a n d a r d s i n t h e s e s t u d i e s , i n t e g r a t i o n o f t h e GLPs i n t o c h e m i c a l f a t e and e n v i r o n m e n t a l s t u d i e s w i l l be e a s i e r . This b r i n g s us t o a n o t h e r impact o f t h i s new r e g u l a t i o n , t h e development of a Q u a l i t y A s s u r a n c e U n i t (QAU) t o m o n i t o r t h e s e s t u d i e s . The

Q u a l i t y Assurance

Unit

The GLPs r e q u i r e the l a b o r a t o r y t o e s t a b l i s h an independent QAU t o m o n i t o r s t u d y conduct and a u d i t the f i n a l r e p o r t . T h i s r e q u i r e m e n t i s needed t o a s s u r e management and the government t h a t the s t u d y i s b e i n g conducted a c c o r d i n g t o t h e GLP r e g u l a t i o n s and t h a t the

Garner and Barge; Good Laboratory Practices ACS Symposium Series; American Chemical Society: Washington, DC, 1988.


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reported r e s u l t s a c c u r a t e l y p o r t r a y data c o l l e c t e d f o r that study. Expanding e x i s t i n g r e g u l a t i o n s w i l l r e q u i r e t h e f o r m a t i o n o f s p e c i a l i z e d Q u a l i t y A s s u r a n c e U n i t s t h a t c a n a d d r e s s t h e unique needs o f e n v i r o n m e n t a l and c h e m i c a l f a t e s t u d i e s , and implement a program t o m o n i t o r t h e s e s t u d i e s . The purpose o f t h e QAU i s t o ensure study i n t e g r i t y by m o n i t o r i n g t h e s e s t u d i e s from t h e a p p l i c a t i o n o f t e s t s u b s t a n c e , through c o l l e c t i o n o f specimens o r samples, t o t h e c h e m i c a l a n a l y s i s , and t o ensure t h e a c c u r a c y o f data i n the f i n a l r e p o r t . The GLPs a l s o s t a t e t h a t t h e QAU must i n s p e c t each c r i t i c a l phase o f t h e s t u d y . In conducting i n s p e c t i o n s to assess the a n a l y t i c a l c h e m i s t r y phase o f t h e s e s t u d i e s , i t i s i m p o r t a n t f o r t h e QAU t o i d e n t i f y how t h a t phase f i t s i n t o t h e o v e r a l l study p l a n . T h i s knowledge d i r e c t s t h e i n s p e c t i o n by d e t e r m i n i n g what t o l o o k f o r and where t o l o o k . B a s i c q u e s t i o n s t h a t any QAU s h o u l d a s k i n p l a n n i n g an e f f e c t i v e i n s p e c t i o n a r e g i v e n i n T a b l e I .

Table I .

P l a n n i n g an E f f e c t i v e I n s p e c t i o n

•

Is t h i s the beginning, middle,

•

I s t h e purpose o f t h e s t u d y t o d e t e c t o r t o measure (qualitative vs. quantitative analysis)?

•

What t y p e s o f a n a l y s e s a r e b e i n g conducted?

•

What type o f equipment i s s p e c i f i e d

•

What a r e t h e c a l i b r a t i o n o r QC r e q u i r e m e n t s , r e c o v e r y , and c o n t r o l l i m i t s ?

•

What a r e t h e d e t e c t i o n l i m i t s f o r t h e v a r i o u s a n a l y s e s ?

•

What p r o c e d u r e s identification?

•

Who i s r e s p o n s i b l e f o r c o n d u c t i n g t h e a n a l y s e s and what i s h i s or her t r a i n i n g ?

•

Where a r e t h e SOPs kept at a l l times?

•

Where a r e samples r e c e i v e d and s t o r e d ?

•

Where a r e t h e d a t a

a r e used

o r end o f t h e p r o j e c t ?

t o ensure

i n t h e p r o t o c o l o r SOP? including

sample c u s t o d y

frequency,

and sample

and a r e they a c c e s s i b l e t o t h e s t a f f

stored?

When c o n d u c t i n g an assessment o f an o u t s i d e l a b o r a t o r y , t h e adequacy o f t h e l a b o r a t o r y ' s QAU and i t s r e l a t i o n s h i p t o management s h o u l d be d e t e r m i n e d i n a d d i t i o n t o a s s e s s i n g t h e l a b o r a t o r y operations. Q u e s t i o n s d i r e c t e d toward e v a l u a t i n g t h e QAU might i n c l u d e t h o s e i n T a b l e I I . I t i s o f t e n h e l p f u l f o r t h e QAU t o make up a c h e c k l i s t ; however, t h e l i s t s h o u l d be f l e x i b l e and open-ended so t h a t i t c a n i n c o r p o r a t e u n a n t i c i p a t e d e v e n t s .



78 Table I I .


•

I s there

Evaluation

o f Laboratory Q u a l i t y Assurance

Unit

an independent QAU on s i t e ?

•

To whom does t h e QAU r e p o r t ?

•

What i s t h e background o f t h e QAU s t a f f , and i s t h e s t a f f adequate t o c o v e r t h e amount and t y p e o f work b e i n g conducted?

•

How does t h e QAU h a n d l e the M a s t e r Schedule? (A s c h e d u l e r e q u i r e d by t h e government s p e c i f y i n g each s t u d y by c h e m i c a l , t y p e , and d a t e s o f c o n d u c t . )

•

Does t h e QAU have SOPs d e s c r i b i n g i n s p e c t i o n and a u d i t i n g procedures?

On e n t e r i n g t h e l a b o r a t o r y , t h e r e a r e s e v e r a l r u l e s o f conduct f o r i n s p e c t o r s t h a t w i l l h e l p t h e QAU i n c o n d u c t i n g a s u c c e s s f u l evaluation. Some R u l e s o f Conduct a r e p r e s e n t e d i n T a b l e I I I . Awaren e s s o f p r o c e d u r e s used by i n s p e c t o r s w i l l h e l p t h e a n a l y t i c a l c h e m i s t t o a n t i c i p a t e q u e s t i o n s t h a t might be asked by t h e i n s p e c t o r .

Table I I I .

R u l e s o f Conduct f o r

Inspections

•

As t h e i n s p e c t o r , y o u a r e t h e r e or i n t i m i d a t e .

t o o b s e r v e and n o t t o i n t e r f e r e

•

Never i n t e r r u p t a t e c h n i c i a n c o n d u c t i n g a d e l i c a t e p r o c e d u r e w i t h a q u e s t i o n t h a t c a n w a i t u n t i l t h e p r o c e d u r e i s complete.

•

Be o b s e r v a n t f o r t h e u n e x p e c t e d , e i t h e r good o r b a d .

•

Never assume; a s k f o r t h e SOP, and check i t t o be s u r e t h a t i t i s t h e same copy t h a t i s i n t h e QAU. F o l l o w t h e p r o c e d u r e i n the SOP as i t i s b e i n g c o n d u c t e d .

•

Review maintenance and c a l i b r a t i o n o f equipment, p l a c i n g s p e c i a l emphasis on QC a c c e p t a n c e c r i t e r i a . T h i s c a n be a c c o m p l i s h e d by r e v i e w i n g c o n t r o l c h a r t s , p e r c e n t r e c o v e r y , p a r a l l e l t e s t i n g o f new s t a n d a r d s , and maintenance l o g s .

•

Review t h e documentation o f t r a i n i n g f o r t h e s t a f f . T h i s can be done by r e v i e w i n g c u r r i c u l u m v i t a e , j o b d e s c r i p t i o n s , p r o f i c i e n c y t e s t i n g r e c o r d s , e d u c a t i o n , and i n - h o u s e t r a i n i n g .

When c o n d u c t i n g an i n s p e c t i o n , s e v e r a l t a r g e t a r e a s must be evaluated. C o n t r o l l i m i t s o r " c h a r t s " a r e h e l p f u l and s h o u l d be e s t a b l i s h e d by p l o t t i n g t h e d e f i n e d l i m i t s o f a c c e p t a b l e q u a l i t y control. These c h a r t s a r e i m p o r t a n t t o o l s f o r a s s e s s i n g l a b o r a t o r y p r e c i s i o n , a c c u r a c y , and r e p r o d u c i b i l i t y . They c a n be based on a c u r v e e s t a b l i s h e d from t h e h i g h , mid, and low c o n c e n t r a t i o n s o f a standard analyte. E i t h e r the mid l e v e l o r t h e a v e r a g e o f t h e t h r e e c o n c e n t r a t i o n s t h e n becomes the m i d - l i n e f o r t h e c o n t r o l c h a r t . Acceptable l e v e l s of f l u c t u a t i o n f o r routine mid-level standards,


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s p i k e s , and b l a n k s can then be i d e n t i f i e d and drawn onto the c h a r t . C o n t r o l c h a r t s can a l s o m o n i t o r p e r c e n t r e c o v e r y and r e p r o d u c i b i l i t y or p r e c i s i o n . The f r e q u e n c y s u g g e s t e d by the N a t i o n a l Bureau of S t a n d a r d s f o r c o n t r o l , m i d - l e v e l s t a n d a r d s , b l a n k s , and s p i k e r u n s s h o u l d e q u a l about 5-10 p e r c e n t o f the sample l o a d ( 6 ) . Posted c o n t r o l c h a r t s m a i n t a i n e d d a i l y can g i v e s u b s t a n t i a l i n f o r m a t i o n , i n c l u d i n g the f o l l o w i n g : •

I n s t a n t f e e d b a c k t o the t e c h n i c a l s t a f f on a c c e p t a b l e r u n s , d r i f t , and o u t - o f - c o n t r o l s i t u a t i o n s .

•

A h i s t o r i c a l record

•

V e r i f i c a t i o n o f t e c h n i c a l p r o f i c i e n c y and between d i f f e r e n t s t a f f .

of i n s t r u m e n t

operation. variation

Sample c u s t o d y , more f o r m a l l y r e f e r r e d t o as C h a i n - o f - C u s t o d y p r o c e d u r e s , s h o u l d be d e s c r i b e d i n an SOP and r e v i e w e d . These p r o c e d u r e s a r e n e c e s s a r y to ensure sample i n t e g r i t y and i d e n t i f i c a t i o n from c o l l e c t i o n t h r o u g h t r a n s p o r t t o the l a b o r a t o r y , t o subsequent a n a l y s i s and r e p o r t i n g . V a r i o u s methods can be used from h a n d - w r i t t e n s h e e t s on w h i c h l o g g i n g - i n and o u t , s t o r a g e , and r e s p o n s i b l e p e r s o n n e l a r e i n d i c a t e d , to c o m p u t e r i z e d bar code s e t u p s , to more s t r i n g e n t systems i n w h i c h s e a l e d v i a l s a r e u s e d . Whatever system i s used, i t s h o u l d be adequate f o r the o p e r a t i o n and s p e c i f i e d e i t h e r i n an SOP o r a s t u d y - s p e c i f i c p r o t o c o l o r work plan. Another area needing c l o s e review during i n s p e c t i o n s i s l a b e l i n g and t r a c k i n g o f r e a g e n t s and s o l u t i o n s . A l l r e a g e n t s and s o l u t i o n s s h o u l d be r e v i e w e d t o e n s u r e t h e i r i n t e g r i t y , s t a b i l i t y , and p r o p e r l a b e l i n g . A c c o u n t a b i l i t y , i n t e g r i t y , and s t a b i l i t y can be documented by e s t a b l i s h i n g a r e a g e n t and s o l u t i o n l o g book. It s h o u l d i n d i c a t e l o t number, e x p i r a t i o n d a t e , s t o r a g e r e q u i r e m e n t s , grade of m a t e r i a l used, and d i s p o s a l . Each r e a g e n t and s o l u t i o n s h o u l d be l a b e l e d t o i d e n t i f y c o n t e n t , p r e p a r a t i o n d a t e , e x p i r a t i o n d a t e , s t o r a g e r e q u i r e m e n t s , and p e r s o n who p r e p a r e d the s o l u t i o n . At the end o f the i n s p e c t i o n , i t i s h e l p f u l t o h o l d a d e b r i e f i n g w i t h the P r o j e c t Manager. T h i s i s i m p o r t a n t because i t i n i t i a t e s a d i a l o g u e and e s t a b l i s h e s a l o o p o f communication between the QAU and the P r o j e c t Manager or Study D i r e c t o r . M i s i n t e r p r e t a t i o n s can be i d e n t i f i e d o r a d d i t i o n a l d a t a can be added t o the r e p o r t . S u g g e s t i o n s f o r c o r r e c t i v e a c t i o n can be g i v e n i n an i n f o r m a l way. T r u e GLP i s s u e s can be d i s t i n g u i s h e d from s c i e n t i f i c q u e s t i o n s or suggestions. U s u a l l y , the need f o r f u t u r e i n s p e c t i o n s can be d i s c u s s e d and a s c h e d u l e d e t e r m i n e d . The QAU must then w r i t e an I n s p e c t i o n R e p o r t and send i t t o the P r o j e c t Manager. The w r i t t e n I n s p e c t i o n Report s h o u l d be complete and o b j e c t i v e . Suggested c o n t e n t i s g i v e n i n T a b l e IV. The P r o j e c t Manager r e s p o n d s t o the i n s p e c t i o n r e p o r t i n w r i t i n g , i d e n t i f y i n g agreement o r d i s a g r e e m e n t w i t h the f i n d i n g s and i n d i c a t i n g c o r r e c t i v e a c t i o n ; t h i s c l o s e s the communication l o o p . The completed r e p o r t i s then forwarded t o the D i r e c t o r o f the L a b o r a t o r y or o t h e r a p p r o p r i a t e p e r s o n n e l t o complete the m o n i t o r i n g p r o c e s s or communication l o o p on a h i g h e r l e v e l . GLPs a l s o s p e c i f y t h a t the QAU must conduct an a u d i t on the f i n a l report. I f the i n s p e c t i o n phase has been c o n d u c t e d p r o p e r l y ,


80



T a b l e IV.

C h a r a c t e r i s t i c s o f a Good I n s p e c t i o n Report

•

I t s h o u l d s t a n d on i t s own.

•

I t s h o u l d i d e n t i f y t h e s t u d y , phase i n s p e c t e d , d a t e s o f i n s p e c t i o n , items r e v i e w e d , and s u p p o r t i n g d a t a .

•

I t should c l e a r l y

•

I t s h o u l d i d e n t i f y t h o s e a r e a s where improvement i s s u g g e s t e d and methods f o r improvement.

•

I t s h o u l d be worded such t h a t t h e i n s p e c t i o n p r o c e d u r e i s a p o s i t i v e , u s e f u l e x p e r i e n c e f o r the l a b o r a t o r y .

•

I t s h o u l d i n d i c a t e the time o f the next i n s p e c t i o n , when c o r r e c t i v e a c t i o n has been i n d i c a t e d .

i d e n t i f y a r e a s o f c o m p l i a n c e and

noncompliance.

especially

the a u d i t s h o u l d not be too time consuming. When c o n d u c t i n g the f i n a l r e p o r t a u d i t , the QAU must r e c o n s t r u c t the s t u d y t o a s s u r e t h a t a l l the p i e c e s a r e i n p l a c e and t h a t the s t u d y i s complete. There a r e s e v e r a l ways t o v e r i f y s t u d y i n t e g r i t y ; however, b a s i c a l l y a l l a u d i t s are d i v i d e d i n t o three p a r t s . 1.

The o b j e c t i v e and scope o f the s t u d y a r e d e t e r m i n e d by r e v i e w i n g t h e p r o t o c o l and r e l e v a n t SOPs.

2.

The raw d a t a a r e r e v i e w e d and c o m p l e t e n e s s .

3.

The raw d a t a a r e compared a g a i n s t to e n s u r e a c c u r a t e p r e s e n t a t i o n .

f o r proper

documentation

the f i n a l

report

T h i s l a s t p a r t o r phase i s t r a d i t i o n a l l y thought o f as " t h e audit." I t can be a c c o m p l i s h e d i n two b a s i c ways: e i t h e r u s i n g a random number s t a t i s t i c a l approach o r by a p e r c e n t a g e o r l i n e approach. I n c o n d u c t i n g an a u d i t , i t i s i m p o r t a n t t o remember t h a t some t y p e s o f e r r o r s ( u s u a l l y the s m a l l ones) a r e random, f o r example, a s i m p l e t r a n s c r i p t i o n e r r o r a t the end o f a l o n g c a l c u l a t i o n , w h i l e o t h e r s f o l l o w p a t t e r n s and can have a c u m u l a t i v e impact, such as an u n a c c e p t a b l e c a l i b r a t i o n c u r v e o r even sample mix-up. At the end o f the a u d i t , a F i n a l Report N a r r a t i v e i s w r i t t e n by the QAU t o the P r o j e c t Manager. The format o f the N a r r a t i v e i s s i m i l a r t o t h a t o f the I n s p e c t i o n R e p o r t . Once a g a i n the P r o j e c t Manager responds i n w r i t i n g , thus e s t a b l i s h i n g a l o o p ; the completed N a r r a t i v e i s then forwarded t o upper management. The GLPs s p e c i f y t h a t the f i n a l r e p o r t i n c l u d e a QA Statement l i s t i n g the d a t e s o f i n - p r o g r e s s i n s p e c t i o n s , when they were s e n t t o the Study D i r e c t o r o r P r o j e c t Manager, and when t h e y were s e n t t o upper management. T h i s statement i s t o be s i g n e d by the QAU. The QA Statement s h o u l d not be c o n f u s e d w i t h the GLP r e q u i r e m e n t f o r a Compliance Statement. T h i s statement v e r i f i e s GLP c o m p l i a n c e , and i s to be s i g n e d by the Study D i r e c t o r o r P r o j e c t Manager. Because o f p o t e n t i a l c o n f u s i o n o v e r t h e s e two s t a t e m e n t s , the F i n a l Report N a r r a t i v e s h o u l d a d d r e s s a l l a r e a s o f the r e p o r t , and produce a w r i t t e n d i a l o g u e between the Study D i r e c t o r , the P r o j e c t Manager,


12. ROYAL


81

and the QAU. By a d d r e s s i n g any problems i n w r i t i n g and by the Study D i r e c t o r r e s p o n d i n g i n w r i t i n g , the d i s t i n c t i o n between t h e s e two r e q u i r e d s t a t e m e n t s can be c l a r i f i e d . The r e s p o n s i b i l i t y t o m o n i t o r the study and r e p o r t on c o m p l i a n c e i s t h a t of the QAU; the r e s p o n s i b i l i t y to conduct the s t u d y i n c o m p l i a n c e w i t h the r e g u l a t i o n i s t h a t o f the Study D i r e c t o r .


Discussion E n l a r g i n g the scope o f the GLPs t o i n c l u d e e n v i r o n m e n t a l and c h e m i c a l f a t e s t u d i e s w i l l have a s u b s t a n t i a l impact on the conduct of such studies. Implementation o f t h i s r e g u l a t i o n t o i n c l u d e f i e l d t e s t i n g programs w i l l b r i n g new c h a l l e n g e s to e x i s t i n g QAUs. However, by d e f i n i n g the scope, the o b j e c t i v e s , and r e s p o n s i b i l i t i e s , and by r e l y i n g on p a s t e x p e r i e n c e , we can b e g i n t o i d e n t i f y ways t o meet that r e s p o n s i b i l i t y . As the r e g u l a t i o n becomes e f f e c t i v e , i t w i l l be i m p o r t a n t f o r EPA to e x p l o r e the i n t e g r a t i o n o f the GLP r e g u l a t i o n w i t h e x i s t i n g r e g u l a t i o n s commonly used f o r the C o n t r a c t L a b o r a t o r y Program (CLP). The CLP program o p e r a t e d by EPA r e g u l a t e s l a b o r a t o r i e s c o n d u c t i n g c h e m i c a l a n a l y s e s under the Resource C o n s e r v a t i o n and Recovery A c t (RCRA) and Superfund programs (4_) (7) . They must i d e n t i f y o v e r l a p , as w e l l as d i f f e r e n c e s , because many l a b o r a t o r i e s w i l l be o p e r a t i n g under b o t h r e g u l a t i o n s . L a b o r a t o r i e s c e r t i f i e d under the CLP may t h i n k t h a t they a r e i n c o m p l i a n c e w i t h GLPs and not r e a l i z e the d i f f e r e n c e s i n the r e g u l a t i o n s . The CLP program i s used to e v a l u a t e l a b o r a t o r i e s c o n t r a c t e d t o a n a l y z e h a z a r d o u s waste, w h i l e the FIFRA/GLP program r e g u l a t e s the conduct o f s t u d i e s used to s u p p o r t the r e g i s t r a t i o n o f p e s t i c i d e s . Thus, i t i s c o n c e i v a b l e t h a t some a n a l y s e s may be r e g u l a t e d under b o t h programs. Whereas the CLP program s p e c i f i e s methodology and QC r e q u i r e m e n t s , the GLP r e g u l a t i o n s t r e s s e s r e c o r d k e e p i n g and d a t a a c c o u n t a b i l i t y . In the p a s t , the q u a l i t y and i n t e g r i t y of e n v i r o n m e n t a l and c h e m i c a l f a t e s t u d i e s have v a r i e d c o n s i d e r a b l y . W h i l e I am not recommending the development of a l a b o r a t o r y c e r t i f i c a t i o n program or mandatory methodology, the p o t e n t i a l p r a c t i c a l i n t e g r a t i o n of the CLP and GLP r e g u l a t i o n s c o u l d have a s u b s t a n t i a l impact on the way e n v i r o n m e n t a l and c h e m i c a l f a t e s t u d i e s have been c o n d u c t e d . P r a c t i c a l i n t e g r a t i o n c o u l d improve the q u a l i t y o f t h e s e s t u d i e s i n the f u t u r e . T o g e t h e r , t h e s e r e g u l a t o r y programs c o u l d r e s u l t i n a system t o document methods and a s s e s s d a t a i n t e g r i t y so t h a t the r e l i a b i l i t y of the r e s u l t s and c o n d i t i o n s under w h i c h they were produced c o u l d be v e r i f i a b l e i n a way t h a t would e n s u r e a c c u r a c y , r e p r o d u c i b i l i t y and s u c c e s s f u l l e g a l r e v i e w . The outcome of such a system would enhance s c i e n t i f i c a c c e p t a n c e , c r e d i b i l i t y , and p u b l i c confidence. Summary A p p l y i n g GLP p r i n c i p l e s t o f i e l d s t u d i e s and a n a l y t i c a l c h e m i s t r y operations w i l l r e q u i r e i d e n t i f y i n g those operations that are u n i q u e to the t y p e of s t u d y and d i s c i p l i n e . In t h i s r e g a r d , the importance of c r e a t i v e l y a d a p t i n g p r i n c i p l e s d e v e l o p e d from i n - h o u s e m o n i t o r i n g s i t u a t i o n s to f i e l d s t u d y o p e r a t i o n s has been d i s c u s s e d . The d i f f e r e n c e s between QC and QA have been d e f i n e d . Inspection




82

and a u d i t p r o c e d u r e s have been e v a l u a t e d . The importance o f e s t a b l i s h i n g p r a c t i c a l C h a i n - o f - C u s t o d y p r o c e d u r e s and Q u a l i t y C o n t r o l s t a n d a r d s has been r e v i e w e d , as w e l l as t h e importance o f b l e n d i n g t h i s r e g u l a t i o n w i t h e x i s t i n g r e g u l a t i o n s , and the r o l e o f the Q u a l i t y A s s u r a n c e U n i t i n m o n i t o r i n g t h e s e t y p e s o f s t u d i e s . The development o f GLP compliance programs t o m o n i t o r e n v i r o n m e n t a l s t u d i e s programs i s s t i l l i n i t s i n f a n c y . A l t h o u g h the i n i t i a l purpose o f t h i s r e g u l a t i o n i s t o p r o v i d e a mechanism f o r e n s u r i n g p r o p e r conduct and a c c u r a t e r e p o r t i n g o f d a t a c o l l e c t e d f o r e n v i r o n m e n t a l f i e l d t e s t i n g programs used t o s u p p o r t r e g i s t r a t i o n of p e s t i c i d e s and c h e m i c a l s , i t s p o t e n t i a l a p p l i c a t i o n w i l l undoubtedly go beyond t h e s e a c t i v i t i e s . We a r e a l r e a d y s e e i n g GLP r e c o r d k e e p i n g p r i n c i p l e s b e i n g a p p l i e d t o m u n i c i p a l and i n d u s t r i a l p o l l u t i o n m o n i t o r i n g programs, E n v i r o n m e n t a l Impact Statements, RCRA/Superfund o p e r a t i o n s and c o u r t r e v i e w . B a s i c p r i n c i p l e s of good r e c o r d k e e p i n g and documentation a r e fundamental t o t h i s r e g u l a t i o n and t o good s c i e n c e , and a r e t h e r e f o r e u n i v e r s a l i n t h e i r application.

Literature Cited 1. 2. 3. 4. 5. 6. 7.

The Good Laboratory Practices, FDA, 1987, FR 43, No. 247. The Good Laboratory Practices, FIFRA/EPA, 40 CFR, Part 160. The Good Laboratory Practices, TSCA/EPA, 40 CFR, Part 792. Guidelines Establishing Test Procedures for the Analysis of Pollutants Under the Clean Water Act, 40 CFR, Part 136. Kateman, G.; Pijpers, F.W. Quality Control in Analytical Chemistry; John Wiley & Son: New York, 1981. Principles of Quality Assurance of Chemical Measurements, U.S. Department of Commerce, 1985, NBS-SIR 85-3105. Identification and Listing of Hazardous Waste, 40 CFR, Part 261.

RECEIVED January 29, 1988


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