Schieffelin indicated they would not withdraw the product from the market and preferred to see the outcome of a showdown on patents.

Mr. Hammer said Schering proposes to increase the strength of their DH liquid (dihydroxy-estrin) from 1 mg. in 10 cc. to 3 mg. in 10 cc. The proposal, he said, was to increase the strength without any increase in price or notice to the trade. He further said his concern would like to put pregneninonal on the market without delay especially in view of their very favorable clinical reports.

There was some discussion by Dr. Oppenheimer and Messrs. Burgher and Walton Bobst. The last named asked about the ratio of the preparation to progesterone. Mr. Kamp held that were "all the data in our possession" to be put before the government, the preparation would not be accepted.

Mr. Hammer said his concern was definitely interested in introducing the product October 1, 1939, and would like to have a discussion on prices so that there would be a clear understanding by all the parties as to Schering's intention of marketing Proluton C by October 1st.

Doctor Oppenheimer said he thought we should go slow with such a preparation so as to not injure our reputation.

Mr. Kamp said he could not commit himself on prices.

Doctor Josephy brought out that the dose is 10 times that of progesterone. He suggested putting the matter over to the time of the next meeting.

Mr. Hammer said he would like to have the gentlemen consider the proposal. He said they have some favorable clinical reports on the substance.

Doctor Oppenheimer suggested "Anhydroxy-progesterone" as a proper name for the substance. He said that side-effects had been observed with daily doses of 3x5 mg. and 3x10 mg.

Mr. Hammer said they were considering marketing both a 5-mg. and 10-mg. dose in units of 12.

Mr. Kamp then brought up the subject stilboestrol.

Mr. Hammer said he thought that any concern would have a hard time getting stilboestrol accepted in this country.

Doctor Oppenheimer pointed out that in this country estradiol prices may not be too much out of line with those of stilboestrol compared with Great Britain. The question of side-effects from stilboestrol was then discussed.

Doctor Josephy told of reports from Amsterdam on the use of stilboestrol in animal experimentation. He said that he thought the government would look not only at the favorable reports on a preparation which was submitted but also the unfavorable ones.

Mr. Kamp said that he thought some concern had already filed with the government a request to market stilboestrol.

Mr. Walton Bobst wanted to know whether there was anything new concerning the British Drug House estroform which is being widely sold in Canada and was being analyzed by Bloomfield for estradiol content.

Mr. Hammer discussed the matter and said that he thought analysis showed the preparation to be estradiol.

Mr. Hammer then told the conference that his concern would like to introduce an additional package of 50 ampuls of Progynon-B either as single packages of 50 or in double cartons (twin packages).

Mr. Kamp said he knew of no objections.

The price of the proposed Schering package is in line with the products of the other 2 concerns.

Mr. Walton Bobst asked whether the time was appropriate for a discussion of the 2 smaller dosage forms of estradiol.

Mr. Kamp said that he thought all would eventually come to stating potency in even milligrams.

Mr. Walton Bobst asked about figuring prices on milligram basis.

Mr. Hammer suggested that final action be deferred until a plan could be submitted on the basis of actual milligram content. In this the Conference agreed.

Mr. Walton Bobst then brought up the subject of Doctor Newcomb's N. W. D. A., to the proposed direct retail account policy.

The matter was discussed by various members of the Conference with the decision reached to each handle the situation as best possible, individually, rather than collectively.

The conference adjourned at 4: 10 P. M.

E. A. W.

84949-44-pt. 10

MEETING WITH ROCHE-ORGANON AND CIBA REPRESENTATIVES, AUGUST 1, 1939

1. Roche-Organon said to operate as a separate organization entirely. Order quotations are separate and distinct and cannot include any Hoffmann-La Roche iems with exception of promotion. Billing is separate and accounts are separate. (a) Hoffmann-La Roche detail men, however, do detail Roche-Organon products-"At least they are supposed to," says Walton Bobst.

II. Manufacturer-Wholesaler agreement of Hoffmann-La Roche does not include Roche-Organon but it exerts considerable effect in maintaining the RocheOrganon schedule. Elmer Bobst says they hold the Hoffmann-La Roche contract over them as a threat.

III. Wholesaler contracts are said to be legal. So far, there has been no test case to prove them. This was questioned by Mr. Kamp.

IV. Roche-Organon does not have a manufacturer-retailer contract on RocheOrganon products. They do have a manufacturer-retailer agreement on Hoffmann-La Roche products.

V. The Ciba line is generally being sold through the wholesaler at various discounts, sometimes 10-15%. Ciba reluctant to make contracts with the wholesaler because they feel that will react to their disadvantage through the trade. No decision on this point.

VI. Testosterone Propionate.-What is our set-up on the "propionate" with regard to Squibb, Winthrop, and Armour activities?

VII. Ciba is being urged by Bobst to go on a wholesaler contract, or in some other way to restrict inside discounts. Otherwise it will be necessary for RocheOrganon and ourselves to condone discounts on professional products. Ciba is to seek means to avoid inside discounts.

VIII. Ciba's physicians' prices based on a survey with Ciba representatives. The average is 15% over the druggists' cost. They will make an adjustment to 20% to equal ours and Roche-Organon's.

IX. All three concerns are to have common prices, discounts, and terms. We are also to think of joint promotion plans for the general benefit of the hormone lines.

X. Terms.-Roche-Organon has a $75.00 minimum order ($60.00 net initial order) and the same on reorder quantities. Ciba has a minimum initial order of $75.00 net (all items included). Cannot see their way clear to insist on reorders of $75.00.

XII. New Accounts. All three firms agree to a total amount of 150 prescription accounts and will exchange lists.

(a) Merchandising chain accounts are not included in the counting. Prescription chain accounts such as Horton and Converse would be included as one unit. Organizations such as Liggett would not be included in the 150.

XIII. On drop shipments to druggists, Ciba does not allow a discount to jobbers except on very large sizes. They have had rather good results with this plan with few objections.

XIV. We will provide two lists; one containing wholesalers, that is, all accounts we sell wholesale, and the second list containing retailers only or prescription accounts. (We would also supply them if necessary with a list of chains and department stores.)

XV. Hoffmann-La Roche insists upon $100.00 orders from wholesalers.

XVI. DH Solution is to be considered in higher potency. Schering would like to increase strength from .1 mg. to .3 mg. at the same price. No announcement to the trade. All agreed.

XVII. Pregnanin tablets 5 bg. and 10 mg. Schering would like to introduce. Dr. Oppenheimer (Ciba) has had a number of bad reports in this country and will send us a summary of the bad results he has had. The Ciba product is generally used in a ratio of six to one (progesterone); Roche-Organon ten to one. Kamp says government will not permit it to be used. Dr. Josephy says his reports look good. We want them to consider a tentative schedule which Kamp will discuss when in Basle. Another name which Dr. Oppenheimer says is better is ANHYDROXYPROGESTERONE.

XVIII. Stilboestrol.-Ciba and Roche-Organon want to have it just to be able to knock it with physicians. They say the hormone business in England has been destroyed just by this new product. On the other hand, it is said to injure the liver and there is doubt that the U. S. Government will allow it to be used.

XIX. Progynon-B Ampules. We are to consider the introduction of a 50ampule package or two 50's in one carton. This is satisfactory with Ciba but we will submit a schedule when the plan is set up.

EXHIBIT No. 206

CONFERENCE, FRIDAY, OCTOBER 27TH, 1939

Present: Mr. Kamp, Mr. E. H. Bobst, Mr. Stragnell, Mr. Peterson, Mr. E. W. Bobst, Dr. Josephy, Dr. Weltzein, Mr. Hammer, Mr. Bernhard, Dr. Oppenheimer, Mr. Storm, Mr. Burgher.

The meeting was called to order at approximately 11:00 A. M.

At the opening of the meeting a new agenda submitted by Mr. Hammer was offered for discussion.

Mr. E. H. Bobst suggested that notes taken during a meeting emphasize the "points developed" so that same may be used for reference purposes at future meetings. Copies of notes taken should be submitted only to Mr. Kemp, Mr. E. H. Bobst and Dr. Weltzein. This suggestion met with the approval of all present. Mr. Hammer brought up for discussion their proposed introduction of 5 mg. and 10 mg. tablets of Pregneninolone on November 1st, 1939.

Mr. Kamp advised that he had no objection to the suggested price for this product despite the low margin of profit necessary when the commercial angle was considered but that he seriously objected to the issuance of two different strength tablets which he considered unnecessary in this particular case.

Mr. E. H. Bobst concurred with Mr. Kamp's objection and emphasized the reluctance of the pharmacist (both wholesale and retail) to placing on his shelves a multiplicity of various sized packages and strengths of any new product. Mr. Burgher also emphasized the criticism of the trade levied on manufacturers for this reason.

Dr. Waltzien commented that in his opinion the introduction of numerous packages was justified by the increase in business which resulted from such introductions. He advocated that the packages issued by the three concerns should not be identical and suggested that one firm be privileged to issue two or more packages or strengths of a product even though the other firms have only one. Mr. Kamp agreed in principle to the package differentiation but pointed out the price difference which would result from such arrangement in favor of the party issuing the lower strength tablet and that he, consequently, advocated the use of either a 5 mg. tablet or a scored 10 mg. tablet by all parties.

Dr. Stragnell advised that the basic work done with the material should bear consideration, and that eighteen months' work with Pregneninolone indicates that there are two distinct uses for the product:

(1) Abortion (threatened or habitual) in which cases a dosage of 2 or 3 mg. a day is needed, and

(2) Dysmenorrhea, in which cases a dosage of 40 to 60 mg. a day is indicated.

In Dr. Stragnell's opinion, in the first indication issuance of a tablet larger than 5 mg. would be commercially wrong whereas in dysmenorrhea, tablets of 10 mg. would be the proper issuance. Dr. Stragnell agreed that in most instances the fewer the number of packages issued the better, but not in this particular case. He felt that the 5 mg. tablet and 10 mg. tablet was a conservative issuance in view of the potential trend for its usage.

Mr. Kamp asked if the dosage varied from 2 mg. to 60 mg. a day why should not a 5 mg. and a 20 mg. tablet be issued.

Dr. Stragnell advised that in his opinion there were two objectives, (1) that of the unit cost to the patient, and, (2) that the administration of the product in divided doses was desirable.

Mr. E. H. Bobst wished to be informed as to what clinical evidence is available as to its value.

Dr. Josephy advised that pregneninolone (for oral administration) replaced Progesterone, and that the product was still in the experimental stage and should be so treated. The chief indication for its use is dysnorrhea.

Dr. Stragnell pointed out its usefulness in pregnancy and the necessity of its administration for a period of seven or eight months in some cases.

Mr. E. H. Bobst advocated the issuance of a divided dose tablet to curtail the cost to the patient.

Dr. Stragnell proposed that they issue what they wished and the others act accordingly.

Dr. Waltzein suggested that if Mr. Bobst desired he could introduce a 10 mg. tablet only, at a 10% price differential under the 5 mg. tablet price.

*A third indication, not specified, for the use of Pregneninolone was also mentioned.

Mr. Bobst (E. H.) advised they would issue a scored 10 mg. tablet.
Dr. Stragnell advised they would issue a 5 mg. and a 10 mg. tablet.

Mr. Kamp reserved decision as to the size tablets he would issue until further study be given the advisability of issuing a 20 mg. tablet as well as a 5 mg. tablet. Mr. Kamp pointed out that in the event of criticism of the relationship between the cost of pregneninolone tablets and progesterone ampules, it could be counted by the explanation as to the loss in efficacy by oral administration, the increased cost of ampule manufacturing, and the statement that two different products are being compared.

Mr. E. H. Bobst advised that he would issue ten 10 mg. tablets instead of twelve at % less the list price of the twelve tablets.

Dr. Stragnell offered objection.

Mr. Kamp and Mr. Bobst pointed out that such issuance would to some extent offset the advantageously low unit price of the 5 mg. tablet.

Dr. Weltzein withdrew their objection to the issuance of the package of ten 10 mg. tablets pregneninolone at %th less than the list price of the package of twelve 10 mg, tablets, provided Mr. Bobst did not issue a 5 mg. tablet.

Dr. Stragnell advised that according to the findings of Corner, pregneninolone was one-fifth as active as progesterone, this ratio determined by animal experiment as well as by clinical results.

Mr. Bobst objected to the sales propaganda use of the definte statement of a 1-to-5 ratio.

Dr. Stragnell stated he saw no objection, in view of Corner's findings. He pointed out that Crone and Hamblin's work showed no nausea and no ill effects following the administration of pregneninolone and advised Dr. Oppenheimer he would forward to him the data referred to above. He suggested that Dr. Oppenheimer check the material being used as he believed the nausea resulting from its administration was due to impurities in the material.

Dr. Josephy advanced the information that Dr. Zondek saw no need for a 5 mg. tablet of pregneninolone and found a 1-to-10 ratio between the product and progesterone.

Dr. Oppenheimer showed work determining a 1-to-6 ratio.

Dr. Stragnell advocated that a "1-to-5 ratio with variations at times" be used for promotional purposes.

Mr. Hammer advised that their physicians' pamphlets were compiled but that he was not sure as to the statement of the ratio made therein. Copies of this pamphlet will be sent to the interested parties for perusal. Mr. Hammer also informed those present that the pamphlet issued by them would go forward to physicians in conjunction with other literature and that no individual mailings on pregneninolone were to be made.

Mr. Hammer suggested that a time limit of one month be set for objections to proposals of one of the interested parties.

Mr. E. H. Bobst recommended that this time limit be made flexible depending upon the proposal.

Mr. Kamp advised the time limit set must agree with the contract as far as introduction of new products is concerned which time limit is stipulated as three months.

Mr. E. H. Bobst concurred with Mr. Kamp as far as new products were concerned.

During the discussion Stilboestrol was mentioned and Dr. Weltzien remarked he hoped "none of us will introduce stilboestrol."

Dr. Stragnell wishes to curtail the time limit to one month as far as the issuance of products already on the market is concerned.

Mr. Kamp stated he agreed in principle to this but must insist that the threemonth period be adhered to with reference to introduction of a product not known to Basle even though the product is a known one. Mr. Kamp agreed that if packages are available in one price list the others should be able to introduce them prior to three months. It was advocated by Mr. Kamp that we should advise one another of investigational work as it progresses.

Mr. Peterson pointed out that a member firm should be able to insist that a meeting be held within thirty days if they so desire.

Mr. E. H. Bobst advocated that we expedite changes, give notices promptly and arrange prompt discussions, and that whenever possible we shorten time limits and not insist on the three-month stipulation.

Mr. Kamp asks that we make as few changes in prices as possible in view of the expense involved in reprinting of price lists and reimbursing the trade for stocks on hand. Mr. Kamp drew attention to the fact that the introduction of

new products in America, which products are not introduced in Europe, would probably take longer than three months.

Dr. Josephy requested that meetings should be called promptly.

An agreement was reached that a meeting must be held within one month on request of a member party.

Dr. Weltzein advocated that one firm should be privileged to introduce a new product which is known, such as methyl testosterone, even though objected to by the others. If one concern has evidence that the product produces side actions and another concern has evidence that the product does not produce side actions, such variance in data should not prevent the concern desiring to introduce the product from proceeding in accordance with their desires.

Dr. Stragnell advanced the information that because of the patent situation they proposed to replace their ointment containing free testosterone with an ointment containing methyl testosterone.

Mr. Kamp and Mr. E. H. Bobst offered objection to the introduction of a methyl testosterone ointment on the grounds that it offered no clinical advantage whatsoever over testosterone propionate ointment and that its introduction weakened our combined stand with reference to testosterone propionate, which form is used for injection purposes.

Dr. Stragnell referred to the recent publication of Moore, which work was criticized by Drs. Oppenheimer and Josephy. Mr. Kamp and Mr. Bobst also criticized Moore's report. Dr. Stragnell also referred to work done in England with the oral administration of methyl testosterone and advised that it was his impression that the European agreement extended the privilege to a member concern to use whichever form of testosterone they desired.

It was pointed out that at the time of the agreement referred to no methyl testosterone was available and that methyl testosterone could not be classified as an ester of testosterone.

Mr. Bobst remarked that there was "no need for discussion as our friends apparently fully intend to issue methyl testosterone."

Dr. Stragnell advised that they were only submitting for approval the proposition that they wish to introduce methyl testosterone.

Dr. Josephy informed those present that according to available experiments no proof was established as to the superior efficacy of either free or methyl testosterone over the proprionate.

Recess for lunch.

It was necessary that Dr. Stragnell and Dr. Weltzein leave shortly after the resumption of the meeting. After their departure discussion relative to methyl testosterone was resumed.

Mr. Kamp definitely opposed the issuance of methyl testosterone ointment.

Mr. Bobst also opposed its introduction and asked that Mr. Hammer advise Dr. Stragnell and Dr. Weltzien of the objections. Mr. Bobst also advised Mr. Hammer that he believed it would be in the interests of all concerned if they would issue an ointment of testosterone proprionate instead of the proposed methyl testosterone ointment.

Mr. Hammer assured those present that he would so advise Dr. Stragnell and Dr. Weltzein. Mr. Hammer also remarked that he believed he should advise those present that they "are geared to introduce the methyl testosterone."

Dr. Josephy advised that I. G. has a patent in England and Germany on desoxycorticosterone acetate.

A brief discussion relative to this product was entered into by Mr. Hammer, Mr. Burgher, Mr. E. H. Bobst, and Dr. Josephy.

An agreement was reached by those present that monthly meetings should be held by the scientific and propaganda divisions.

Mr. Kamp offered objection to the frequent changes of packages and prices, again pointing out the expense these changes involve. This in conjunction with

the proposed change in the prices and strengths of estradiol ointment. Mr. Hammer advised that the reason for the proposed changes was the comparison between the list prices of the tablets, ointments, and suppositories which comparison in his belief warranted consideration of the proposed changes.

Mr. Kamp offered objection to the introduction of new strengths of ointment but agreed to a future discussion as to a price reduction.

Mr. Hammer brought up for discussion the 5 percent allowed to the wholesaler on a shipment of merchandise to a hospital, which shipment is invoiced to the wholesaler.

Mr. Kamp pointed out that this 5-percent allowance was simply a handling charge and in his opinion not a condition to be criticized.