Industrial Research and Development: An Academic's Experience

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Industrial Research and Development: An Academic's Experience ROBERT C. LANMAN Department of Pharmacology and Medicine, University of Missouri-Kansas City, Kansas City, MO 64134 DENNIS J. RUNSER Chemical Affairs, Marion Laboratories, Inc., Kansas City, MO 64134

The majority of visiting professor programs arranged between academia and industry give the visiting professor only a few weeks in company surrondings and do not require direct involvement in the work being done. Although much can be gained from such programs, both by academia and industry, they also leave much to be desired. Solutions to industry challenges barely have time to be proposed, let alone tested, and the visiting professor may well see only the particular challenges facing his host-managers in that brief period. Ideally, visiting professor programs would encompass larger and therefore more representative portions of industry's work. Such a program was designed by the authors when they had already completed more than a year in a client-consultant relationship. The client, Dr. Dennis Runser of Marion Laboratories, Kansas City, Missouri, and consultant, Dr. Robert Lanman, Professor of Pharmacology and Medicine, became acquainted during the course of a study concerned with the kinetics of diltiazem (CARDIZEM) which was conducted at the University of Missouri-Kansas City (UMKC). During one of their many discussions, the idea of a visiting professorship was conceived. It quickly became apparent that there was a mutual interest in improved, stronger, university-industrial relationships. For Dr. Lanman's part, a passive, visitor type of experience was not acceptable. Dr. Runser agreed that if his staff were to benefit from this experience, and if the visiting professor were really to gain an understanding of what is required of future graduates entering the job market, a more concentrated and in-depth program would be needed. Thus, plans were formulated to propose an in-house consultant role for the visiting professorship. Once the proposed experience had been formulated, University approval of a sabbatical leave was sought and obtained. Dr. Runser submitted the proposal to upper management, which was also subsequently approved. A c o n t r a c t was drawn up which d e t a i l e d the commitments of each p a r t y . The c o n t r a c t was r e l a t i v e l y simple. F i r s t , i t p h y s i c a l l y provided f o r an o f f i c e w i t h a telephone and s e c r e t a r i a l 0097-6156/84/0244-0013S06.00/0 © 1984 American Chemical Society Runser; Industrial-Academic Interfacing ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on March 31, 2018 | https://pubs.acs.org Publication Date: February 6, 1984 | doi: 10.1021/bk-1984-0244.ch003

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INDUSTRIAL-ACADEMIC INTERFACING

a s s i s t a n c e i n the Chemical A f f a i r s Department a t Marion Laboratori e s . Chemical A f f a i r s i s organized i n t o three departments: Analy t i c a l Research and Chemical S t a b i l i t y , Chemical Development and S c i e n t i f i c Resources, and Biopharmaceutics. Second, i t covered the f i n a n c i a l terms agreed upon, which i n c l u d e d reimbursement f o r t r a v e l expenses i n c u r r e d i n the performance of c o n s u l t i n g d u t i e s . T h i r d , the c o n t r a c t provided t h a t p e r i o d i c r e p o r t s be w r i t t e n as necessary, and t h a t s t r i c t c o n f i d e n t i a l i t y be maintained as w e l l as adherence to Company p o l i c i e s . I t i s important t o recognize that t h i s v i s i t i n g p r o f e s s o r s h i p had the s t a t u s of an independent c o n s u l t a n t or c o n t r a c t o r , not a p a r t - t i m e employee of the Company. This p r o v i s i o n s i m p l i f i e d the arrangement and e l i m i n a t e d the adm i n i s t r a t i v e burden and cost a s s o c i a t e d w i t h an employee s t a t u s . F i n a l l y , statements were i n c l u d e d which allowed e i t h e r p a r t y t o terminate the program w i t h a 30 day n o t i c e . This p r o v i s i o n was made to cover a l l c o n t i n g e n c i e s ; however, i t was never intended to be used. The process of developing the program and c o n t r a c t u a l a r rangements took n e a r l y a year, which i n c l u d e d o b t a i n i n g approval through the r e s p e c t i v e U n i v e r s i t y and Company a d m i n i s t r a t i o n s . The program began i n January, 1982. From the academic p o i n t of view there were s p e c i f i c o b j e c t i v e s to pursue through t h i s research and development experience. The f i r s t r e l a t e d to a d m i n i s t r a t i o n of the graduate program i n the Pharmaceutical Sciences a t the School of Pharmacy. T h i s program o f f e r s e i t h e r the MS or PhD degree i n Pharmaceutical Sciences w i t h research emphasis i n pharmaceutics, pharmaceutical chemistry, pharmacy a d m i n i s t r a t i o n and pharmacology/toxicology. The program i s designed around a core of pharmaceutical science coursework i n tended to assure t h a t a l l graduates have a broad base of pharmac e u t i c a l knowledge i n a d d i t i o n to the e x p e r t i s e developed i n t h e i r chosen areas of research. Since these graduates o f t e n accept posi t i o n s i n the pharmaceutical i n d u s t r y , as w e l l as w i t h government agencies and i n academia, i t was d e s i r a b l e to explore f i r s t - h a n d the s p e c i f i c needs of the pharmaceutical i n d u s t r y , as represented by Marion L a b o r a t o r i e s , w i t h respect to the t r a i n i n g of pharmaceutical scientists. A second o b j e c t i v e a l s o r e l a t e d to graduate education. Often students about to r e c e i v e t h e i r graduate degrees a r e somewhat undecided as to the next step. They f r e q u e n t l y ask questions such as: 1. Should I take a p o s t d o c t o r a l p o s i t i o n ? 2. Should I accept a teaching p o s i t i o n ? 3. Should I seek a p o s i t i o n i n i n d u s t r y ? Frequently, some a c t u a l experience can help when such choices must be made. Thus, i t was decided t o explore the f e a s i b i l i t y of e s t a b l i s h i n g a r e s i d e n c y program i n research and development (R&D) at Marion L a b o r a t o r i e s f o r UMKC pharmaceutical s c i e n c e graduate students. Under t h i s program, graduate students about to embark upon t h e i r careers would have the o p p o r t u n i t y t o compete f o r r e -

Runser; Industrial-Academic Interfacing ACS Symposium Series; American Chemical Society: Washington, DC, 1984.


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Industrial R & D: An Academic's Experience

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sidency p o s i t i o n s i n Marion's R&D Departments and through t h i s mechanism o b t a i n f i r s t - h a n d experience i n the pharmaceutical i n d u s t r y . Such a program can be viewed as being mutually b e n e f i c i a l to Marion L a b o r a t o r i e s and UMKC, p a r t i c u l a r l y w i t h respect t o f u ture recruitment p o t e n t i a l f o r research and development r e l a t e d positions. In these days of t i g h t s t a t e budgets and ever s h r i n k i n g extramural research funds, u n i v e r s i t i e s must seek a d d i t i o n a l sources of support f o r t h e i r programs. The graduate program i n the pharma c e u t i c a l sciences a t UMKC has experienced a c o n t i n u i n g i n c r e a s e i n a p p l i c a t i o n s , and as the program has grown, so has the need f o r research support. Thus, the t h i r d o b j e c t i v e was t o explore the f e a s i b i l i t y of a cooperative research program between Marion Labo r a t o r i e s and the UMKC School of Pharmacy. Such a program would c o n s i s t of School of Pharmacy f a c u l t y and t h e i r graduate students i n v e s t i g a t i n g s p e c i f i c research p r o j e c t s , mutually agreed upon and supported on a p r o j e c t b a s i s by Marion L a b o r a t o r i e s . The l a s t o b j e c t i v e was t o p e r s o n a l l y become i n v o l v e d i n the day-to-day a c t i v i t i e s of research and development a t Marion and gain i n d u s t r i a l experience. On the p a r t of Marion, s e v e r a l o b j e c t i v e s were a l s o l a i d out. These i n c l u d e d : 1. A s s i s t i n g t h e i r M e d i c a l , B i o l o g i c a l , Product Development, and Biopharmaceutics departments i n the p l a n n i n g of p r o j e c t s and data a n a l y s i s . 2. Helping t o develop and implement in-house pharmacokinetic computer modeling and s t a t i s t i c a l a n a l y s i s programs w i t h i n the Biopharmaceutics Department of Chemical A f f a i r s . 3. P r o v i d i n g in-house s t a f f t r a i n i n g i n the form of c l a s s e s , seminars, and/or workshops. 4. A s s i s t i n g w i t h ongoing research and development p r o j e c t s as needed. 5. E v a l u a t i n g the needs of R&D i n terms of how i t operates and what s k i l l s i t s s t a f f needs t o b e t t e r help t r a i n students, which could i n c r e a s e the company's o p p o r t u n i t y t o h i r e more graduates l o c a l l y . This l a t t e r o b j e c t i v e was e n t i r e l y c o n s i s t e n t w i t h the academic o b j e c t i v e s regarding the t r a i n i n g of pharmaceutical s c i e n t i s t s . One means of accomplishing these o b j e c t i v e s was t o spend time w i t h research and development d i r e c t o r s and other Marion management team members t o gain i n s i g h t i n t o the needs, a c t i v i t i e s , and requirements of the d i f f e r e n t operating f u n c t i o n s of Marion's R&D departments. This was accomplished i n a s e r i e s of i n f o r m a l conferences w i t h D i r e c t o r s of Pharmacology, Toxicology, Chemistry, Pharmaceutical Technology, C l i n i c a l Research, Regulatory, Product Development, M e d i c a l Devices, and Marketing. Information was obt a i n e d as t o the s k i l l s sought i n p o t e n t i a l employees, d e s i r a b l e a t t r i b u t e s , most common backgrounds, approximate number of p o s i t i o n s occupied by MS and PhD persons r e l a t i v e t o the t o t a l s t a f f i n an area, and the n e c e s s i t y of a graduate degree over the BS



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degree. Such requirements v a r i e d w i t h the R&D area concerned. I t was r e a s s u r i n g to f i n d that UMKC's program i n the pharmaceutical sciences i s c u r r e n t l y addressing most of the s p e c i f i c e d u c a t i o n a l requirements and s k i l l s that were considered necessary. The p e r c e p t i o n of an R&D residency program f o r graduate s t u dents was found to vary among the s c i e n t i f i c departments at Mari o n . I n the area of pharmaceutical technology, a residency program was looked upon as a v a l i d concept. I n f a c t , there already i s precedence f o r such a program at the undergraduate l e v e l through the Summer BS Pharmacy i n t e r n s h i p program conducted at Marion. The Pharmacology area regarded the residency program as d e s i r a b l e , but f e l t the minimum time necessary to achieve any b e n e f i t was one year. Since Toxicology f e l t the residency p e r i o d would be d i f f i c u l t to c o r r e l a t e w i t h ongoing t o x i c o l o g i c t e s t i n g , combining pharmacology and t o x i c o l o g y i n t o a one-year residency was c o n s i d ered a p o s s i b i l i t y . In g e n e r a l , the f e a s i b i l i t y of e s t a b l i s h i n g r e s i d e n c i e s of t h i s type at Marion L a b o r a t o r i e s was considered to be d i r e c t l y r e l a t e d to the growth r a t e of the research and d e v e l opment e f f o r t of the company and the a b i l i t y to provide enough time so a student could become f a m i l i a r enough w i t h an area to act u a l l y make a c o n t r i b u t i o n . To examine the f e a s i b i l i t y of a cooperative research program between Marion and UMKC, c e r t a i n key questions were d i s c u s s e d . 1. Does your department c u r r e n t l y have any research p r o j e c t s contracted w i t h u n i v e r s i t i e s ? 2. Would such an arrangement be f e a s i b l e i n your area? 3. What problems do you e n v i s i o n i n such an arrangement, i f any? 4. What manner of implementation of a research arrangement would you suggest? In pharmaceutical technology, most research has immediate deadl i n e s and as a r e s u l t not many o p p o r t u n i t i e s f o r cooperative r e search p r o j e c t s e x i s t . S o - c a l l e d "back burner" research p r o j e c t s are few and f a r between. Cooperative o u t s i d e research e f f o r t s i n the area of t o x i c o l o g y would have to be on an "as needed" b a s i s . Much of t o x i c o l o g i c research on pharmaceuticals i s h i g h l y r e g u l a t ed and, thus, i s not c o n v e n i e n t l y accomplished o u t s i d e the indust r i a l s e t t i n g . Pharmacology o f f e r s more p o s s i b i l i t i e s f o r coo p e r a t i v e research p r o j e c t s , p a r t i c u l a r l y c o n t i n u i n g research on drugs already approved f o r human use, but f o r which a d d i t i o n a l i n formation i s d e s i r e d . A p e r s o n a l preference i n the establishment of such a cooperative research e f f o r t i s to begin d i s c u s s i o n s on a p r o j e c t b a s i s through i n t e r a c t i o n s at the l e v e l of the research s c i e n t i s t . Research p r o j e c t s that a r i s e from d i s c u s s i o n s between academic and i n d u s t r i a l s c i e n t i s t s r a t h e r than u n i v e r s i t y and company adminstrators are much more l i k e l y to be s u c c e s s f u l . With such an approach, once a mutually a t t r a c t i v e problem has been i d e n t i f i e d , a p r o t o c o l and budget can be developed, approval sought from management and work begun. A s i m i l a r approach i n funding academic research was taken by the Upjohn Company. As reported i n



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"The Pink Sheet" ( J u l y 19, 1982, T&G-9), at a recent seminar, Jacob S t u c k i , V i c e P r e s i d e n t of Pharmaceutical Research f o r Upjohn, explained, "We f e e l t h a t the best c o l l a b o r a t i o n s are those that i n v o l v e mutual i n t e l l e c t u a l a t t r a c t i o n between our (Upjohn) s c i e n t i s t s and academic s c i e n t i s t s , " Instead of b u i l d i n g an a f f i l i a t i o n w i t h a u n i v e r s i t y v i a a l a r g e s c a l e p r o j e c t , Upjohn plans to b u i l d a r e l a t i o n s h i p from i n d i v i d u a l p r o j e c t s . F i r s t - h a n d experiences i n research and development at Marion L a b o r a t o r i e s were both v a r i e d and i n t e r e s t i n g . They included the opportunity to p a r t i c i p a t e w i t h Marion's R&D Team i n both w r i t t e n and v e r b a l d i a l o g w i t h the Food and Drug A d m i n i s t r a t i o n concerning the approval and r e l e a s e process f o r new drugs. The f r u s t r a t i o n s of preparing w r i t t e n submissions which seemed to address a l l l i k e l y concerns, only to be rewarded by requests f o r a d d i t i o n a l i n f o r m a t i o n or the a p p l i c a t i o n of a d i f f e r e n t s t a t i s t i c a l t e s t , were not t o t a l l y expected. The means of a d j u s t i n g to these necessary expenditures of time and e f f o r t was learned e a r l y . Opport u n i t i e s were a l s o provided to p e r s o n a l l y conduct some in-house research p r o j e c t s . This i n v o l v e d both bench work and the opportun i t y to d i r e c t the l a b o r a t o r y work of some R&D team member. For example, as p a r t of a l a r g e r k i n e t i c study i n humans, the p a r t i t i o n i n g of a new drug between red blood c e l l s and plasma was i n v e s t i g a t e d i n v i t r o . Another study i n v o l v e d the use of a new r a d i o i s o t o p e f a c i l i t y at Marion i n which t o t a l carbon-14 recovery was determined by l i q u i d s c i n t i l l a t i o n counting of b i o l o g i c a l matrices such as whole blood, plasma, u r i n e , and feces f o l l o w i n g a d m i n i s t r a t i o n of a carbon-14 l a b e l e d new drug e n t i t y that a c t s l o c a l l y i n the alimentary t r a c t . This provided the opportunity to gain hands-on experience w i t h a new m i c r o p r o c e s s o r - c o n t r o l l e d l i q u i d s c i n t i l l a t i o n spectrometer. Having had considerable experience w i t h l i q u i d s c i n t i l l a t i o n counting, t h i s opportunity was used to o f f e r t r a i n i n g i n r a d i o i s o t o p e methods to the b i o a n a l y t i c a l s t a f f . S p e c i f i c requests f o r s p e c i a l i z e d data treatment were sometimes r e c i e v e d . For example, on one occasion a request was made to prepare p r o j e c t i o n s of maximum and minimum plasma l e v e l s that one could expect from a s p e c i f i e d intravenous dosing schedule of a p a r t i c u l a r drug. On another occasion, i n f o r m a t i o n was r e quested as to the a p p l i c a t i o n of c r i t e r i a s u i t a b l e f o r i d e n t i f y i n g a n a l y t i c a l standards which are o u t l i e r s and thus should not be i n cluded i n a standard curve. As f o r Marion L a b o r a t o r i e s ' o b j e c t i v e s , a s s i s t a n c e was p r o v i ded i n the planning of at l e a s t two new research and development p r o j e c t s f o r the Biopharmaceutics Department. In working w i t h k i n e t i c data f o r Food and Drug A d m i n i s t r a t i o n submissions, the computer f a c i l i t i e s at Marion were made a v a i l a b l e through p r o v i s i o n of a t e r m i n a l and d i s k storage. By working w i t h data proc e s s i n g and s t a t i s t i c a l personnel, access to s p e c i f i c pharmacokin e t i c subroutines, F o r t r a n program? such as NONLIN, and s t a t i s t i c a l packages such as SAS were streamlined. In connection w i t h t h i s a c t i v i t y , a weekly s e r i e s of lecture/workshops were conducted on



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handling data, which i n c l u d e d curve f i t t i n g techniques and s t a t i s t i c a l a n a l y s i s of pharmacokinetic parameters. Sessions were conducted over an e i g h t week p e r i o d according to a schedule that encompassed c o n t r i b u t i o n s of time from both Marion and the s t a f f . Manual procedures, as w e l l as the use of computer programs, were covered i n t h i s a p p l i e d , r a t h e r than t h e o r e t i c a l , s e r i e s of p r e s e n t a t i o n s . Work was performed on c e r t a i n key p r o j e c t s f o r Mari o n , p a r t i c u l a r l y i n the area of data a n a l y s i s f o r r e g u l a t o r y subm i s s i o n s , and help was provided i n the i n i t i a l screening of a p p l i cants f o r a new p o s i t i o n i n the biopharmaceutics department. The seven month s a b b a t i c a l which was spent as an in-house cons u l t a n t was an i n t e r e s t i n g and rewarding work experience. Marion L a b o r a t o r i e s was t r u e to t h e i r word. They allowed involvement i n s t a f f meetings, p r o t o c o l w r i t i n g , data a n a l y s i s , problem s o l v i n g , p r e p a r a t i o n of government submissions, and d i a l o g w i t h the Food and Drug A d m i n i s t r a t i o n . Freedom was given to pursue the s p e c i f i c o b j e c t i v e s of the s a b b a t i c a l . These were a s t i m u l a t i n g v a r i e t y of experiences which i n c l u d e d the on-and-off pressure s i t u a t i o n s one o f t e n a s s o c i a t e s w i t h i n d u s t r y . However, the pressures were not uncomfortable, but r a t h e r were t o l e r a b l e to the p o i n t of being e x c i t i n g . Most of the o b j e c t i v e s were at l e a s t p a r t i a l l y s a t i s f i e d , and r e t u r n to the academic community occurred w i t h a much more secure a t t i t u d e w i t h respect to the needs of i n d u s t r y f o r pharmaceutical s c i e n t i s t s . Thus, the f e e l i n g was r e i n f o r c e d t h a t a researcher w i t h a broad base of knowledge i n the pharmaceutical science areas of pharmaceutical chemistry, pharmaceutics, pharmacy a d m i n i s t r a t i o n , pharmacology, and t o x i c o l o g y , i n a d d i t i o n to i n depth research e x p e r t i s e i n one of these areas, can be a very important a d d i t i o n to the R&D e f f o r t s of a pharmaceutical company. True, these impressions were l a r g e l y based on experiences at Mari o n L a b o r a t o r i e s , and p a r t i c u l a r l y on a c t i v i t i e s i n the Biopharma c e u t i c s Department. However, the pharmaceutical i n d u s t r y has t r a d i t i o n a l l y employed BS degreed pharmacists i n p r o d u c t i o n and marketing areas and the use of pharmaceutical s c i e n t i s t s i n r e search and development i s a l o g i c a l e x t e n s i o n of t h i s p r a c t i c e . Marion L a b o r a t o r i e s a l s o achieved t h e i r o b j e c t i v e s from the program. S u c c e s s f u l a s s i s t a n c e and c o n t r i b u t i o n was obtained on s e v e r a l p r o j e c t s from p l a n n i n g through data a n a l y s i s . S e v e r a l i n house computer modeling programs were implemented which helped the f i r m reduce i t s o u t s i d e expenditures and improve i t s turnaround time f o r these data h a n d l i n g procedures. In-house t r a i n i n g was c a r r i e d out on a one-for-one t u t o r i a l b a s i s as w e l l as i n a c l a s s room s e t t i n g covering t o p i c s from how to operate s p e c i f i c i n s t r u mentation to b a s i c i n t r o d u c t o r y l e c t u r e s i n pharmaceutical chemi s t r y . From the c o n s u l t a n t s h i p , the o p p o r t u n i t y was made a v a i l able to a s s i s t the f i r m i n t h i s c a p a c i t y i n t e r n a l l y and e x t e r n a l l y as an expert witness at key government hearings. The program was considered a success.



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Comment The approach favored f o r i n v o l v i n g graduate students i n coope r a t i v e research p r o j e c t s would depend upon contacts between f a c u t l y members and members of the i n d u s t r i a l R&D s t a f f . For example, by means of i n i t i a l d i s c u s s i o n s , the R&D group can be made aware of the c a p a b i l i t i e s and e x p e r t i s e of v a r i o u s i n t e r e s t e d f a c u l t y members, and some i n s i g h t as t o the p o t e n t i a l R&D needs can be a t t a i n e d . During d i s c u s s i o n s w i t h R&D D i r e c t o r s at Marion L a b o r a t o r i e s , such i n f o r m a t i o n was f r e e l y exchanged. A t the r e quest of R&D, or upon the person's own i n i t i a t i v e , a f a c u l t y member would develop a p r o t o c o l f o r a requested p r o j e c t o r a p r o j e c t perceived to be worthwhile. Further i n t e r a c t i o n between the f a c u l t y person and an R&D s c i e n t i s t i d e a l l y w i l l lead to a mutua l l y agreed upon research p r o j e c t w i t h subsequent generation of a budget. The graduate student should be i n v o l v e d i n a l l d i s c u s s ions during the p r o j e c t e v a l u a t i o n p e r i o d and take p a r t i n the p r o t o c o l and budget p r e p a r a t i o n . The approach favored i n v o l v e s research support on an i n d i v i d u a l p r o j e c t b a s i s as opposed to prov i d i n g a b l o c k grant t o the academic research u n i t . I n the authors' o p i n o i n s , i n d u s t r i a l - a c a d e m i c cooperative research programs should begin i n t h i s manner and expand as the s i t u a t i o n requires. RECEIVED July 28, 1983


Industrial Research and Development: An Academic's Experience

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