Adverse Reactions

1
Adverse Reactions

• Investigating and Reporting Requirements

EBAA Annual Meeting Seattle, Washington June 20,
2009 Amanda Nerone, CEBT
2
Surgeon Responsibilities

• As an end user
• As the Medical Director of an Eye Bank

3
Outlined Requirements

• End User Joint Commissions Transplantation
  Safety Chapter
• Eye Banks EBAA Medical Standards, EBAA OARRS
  Guidance, FDA Current Good Tissue Practice
  (CGTP), 11/05 FDA MedWatch Form FDA 3500A
  Guidance, FDA draft CGTP Guidance

4
Joint Commission Requirements

• Effective July 1, 2005 applying to organizations
  that store or issue tissue
• Standard PC.17.10 standardized procedures to
  acquire, receive, store and issue tissues
• Standard PC.17.20 records permit traceability
  from source facility or donor to recipient or
  other final disposition
• Standard PC.17.30 defined process to
  investigate adverse events to tissue or donor
  infection

5
Joint Commission

• As part of the Joint Commissions Standards
  Improvement Initiative (SII), all transplant
  related standards were moved into a new chapter
  in the 2009 Accreditation Requirements entitled
  Transplant Safety. The SII strives to
• clarify standards language
• ensure the standards are program-specific
• delete redundant or non-essential standards
• consolidate standards

6
Joint Commission

• PC.17.10 now 2009 Standard TS.03.01.01
• PC.17.20 now 2009 Standard TS.03.02.01
• PC.17.30 now 2009 Standard TS.03.03.01

7
End User Tissue Receipt

• TS.03.01.01 2009 EP 7
• The hospital verifies at the time of receipt that
  package integrity is met and transport
  temperature range was controlled and acceptable
  for tissues requiring a controlled environment.
  This verification is documented.
• TS.03.03.01 2009 EP 4
• The hospital sequesters tissue whose integrity
  may have been compromised...

8
End User Tissue Storage

• TS.03.01.01 EP 5
• The hospital follows the tissue suppliers
  written directions for transporting, handling,
  storing, and using tissue

9
End User Tissue Storage

• TS.03.01.01 EP 8-10
• The hospital maintains daily records to
  demonstrate that tissues requiring controlled
  environments are stored at the required
  temperatures.
• The hospital continuously monitors the
  temperature of...storage equipment used to store
  tissue
• ...Storage Equipment used to store tissues at a
  controlled temperature have functional alarms and
  an emergency back-up plan

10
End User Tracking

• TS.03.02.01 EP 1-6
• Hospital records trace from tissue supplier to
  recipient and from recipient to tissue supplier
  unique tissue ID
• Identifies in writing the materials and related
  instructions used to prepare or process tissues
• Documents dates, times, and staff involved when
  tissue is accepted, prepared, and issued
• Records maintained for a minimum of 10 yrs

11
End User Tracking

• Eye Banks will seek from the end user, per EBAA
  Medical Standard M1.500
• Recipient information for tracking purposes
• Post-operative outcome information between 3-12
  months

12
End User Tracking

• TS.03.02.01 EP 7
• The hospital completes and returns tissue usage
  information cards requested by the tissue
  supplier
• HIPAA regs- A covered entity may use or disclose
  protected health information to...entities
  engaged in the procurement, banking, or
  transplantation of cadaveric...eyes...for the
  purpose of facilitating ...eye...donation and
  transplantation
• 45 CFR 164.512(h)

13
End User Adverse Reactions

• End User reporting responsibilities
• internal for investigation
• to the distributing bank for investigation

14
End User Investigation

• TS.03.03.01 EP 1, 2
• must investigate tissue adverse events, including
  disease transmission or other complications that
  are suspected of being directly related to the
  use of the tissue
• written procedure required

15
End User Reporting

• TS.03.03.01 EP 3
• As soon as the hospital becomes aware of a
  post-transplant infection or other adverse event
  related to the use of the tissue, it reports the
  event to the tissue supplier

16
Eye Bank Receipt of Adverse Reaction

• Under 1271.320, the eye bank must maintain a
  record of complaints in a file designated for
  complaints
• A complaint ... alleges the following
• that the HCT/P has transmitted or may have
  transmitted a communicable disease to the
  recipient of the HCT/P or
• any other problem with an HCT/P relating to the
  potential for transmission of comm. disease...

17
Eye Bank Investigation

• Distributing Bank must notify the Source Eye Bank
  (if different), to coordinate investigation
• Source Eye Bank notifies ocular tissue recovery
  entity, processing entity, storage entity to
  investigate steps performed
• Quarantine other ocular tissue from the same
  donor during investigation
• EBAA OARRS Guidance

18
Eye Bank Investigation

• Obtain from transplanting surgeon
• Possible pre-existing/ pre-disposing conditions
  in recipient
• Intraoperative complications
• Possible sources of contamination (if infection)
• Culture results pre and post-op

19
Eye Bank Investigation

• Obtain from transplanting surgeon of mate tissue
• Mate status
• Mate culture results

20
Eye Bank Investigation

• Examples of potential contributing factors for
  PGF include
• Endo trauma, chamber collapse, intracameral
  injection of toxic of preservative containing
  fluids, TASS, known intraoperative Descemets
  trauma, prolonged vitrectomy, tissue manipulation
  intraoperatively (upside down), rebubbling,
  surgeon experience lt10 cases, poor cut, presence
  of anterior chamber IOL, incision size, number of
  folds, insertion/ folding technique, use of
  forceps, dislocation

21
Eye Bank Investigation

• Examples of potential recipient contributing
  factors for PGF include
• persistent epi defect, persistent elevated IOP,
  marked post-op inflammation, choroidal
  hemorrhage, IOL dislocation, flat anterior
  chamber, ocular surface disease, recurrence or
  persistence of pre-operative infectious
  keratitis, persistent wound leak

22
Eye Bank Investigation

• Eye Bank Records Review
• Type of reaction determines the focus of the
  review
• Outlined in EBAA OARRS Guidance

23
Eye Bank Investigation

• Infection Record review focus
• Possible sources of tissue contamination
• Recovery, Processing Aseptic Technique,
  Sterility of Supplies, Equipment, Environmental
  Controls
• Donor Infection
• Donor screening
• Tissue Evaluation

24
Eye Bank Investigation

• Primary Graft Failure Record Review Focus
• Maintenance of cellular function
• Technician handling recovery, processing
• Tissue evaluation
• Tissue storage donor, tissue
• Time elapsed death to preservation, death to
  surgery

25
Eye Bank Investigation

• EBAA Medical Standard G1.000
• The Medical Director shall receive and review all
  adverse reaction reports, documenting any
  corrective actions he/ she determines are
  indicated.

26
Eye Bank Investigation

• Medical Director Determination of Cause
• QA Department provides for review
• Information obtained from transplanting surgeon
• Mate status
• Eye bank records review summary
• If necessary, Medical Director re-contacts
  surgeon for further investigation

27
Eye Bank Investigation

• Primary Graft Failure Reasonably Likely due
  to tissue if
• a. corneal edema is present from the time of
  keratoplasty
• b. the graft does not clear after 8 weeks AND
• c. no known operative or post-operative
  complications, or underlying recipient conditions
  that would explain the biologic dysfunction
• EBAA OARRS Guidance

28
Eye Bank Investigation

• Examples of potential contributing factors for
  PGF include
• Endo trauma, chamber collapse, intracameral
  injection of toxic of preservative containing
  fluids, TASS, known intraoperative Descemets
  trauma, prolonged vitrectomy, tissue manipulation
  intraoperatively (upside down), re-bubbling,
  surgeon experience lt10 cases, poor cut, presence
  of anterior chamber IOL, incision size, number of
  folds, insertion/ folding technique, use of
  forceps, dislocation

29
Eye Bank Investigation

• Ocular Infection Reasonably Likely Due to
  Tissue if
• Signs of inflammation or infection consistent
  with the infectious agent (pain, redness, loss of
  vision) from or near the operative site within
  one month of implantation.
• Greater likelihood if
• match between donor and recipient cultures
• infection in other recipients of tissue from same
  donor
• failed aseptic technique

30
Eye Bank Investigation

• Infection Proven to Be Due to Tissue
• Confirmation by lab testing (e.g., genotyping,
  PCR, wet prep) that links the infectious agent in
  the recipient with donor samples, or
• When testing is not possible, the presence of the
  same infection in both recipient and donor with
  no identified risk in the recipient

31
Eye Bank Reporting

• EBAA Reporting Requirements, per Med. Standard
  G1.000
• Time Frame for reporting within 30 days
• Mode via On-Line Adverse Reaction Reporting
  System (OARRS)
• Report any communicable or other disease
  reasonably likely or proven to be due to donor
  eye tissue, including infection and biologic
  dysfunction. All systemic disease, whether or
  not suspected to be due to donor tissue.

32
Eye Bank Reporting

• FDA Reporting Requirements, per 1271.350(a)
• Time Frame for reporting within 15 calendar
  days of the initial receipt of the information
• Mode via MedWatch Form FDA 3500A, mailed

33
Eye Bank Reporting

• Report Adverse reactions that involve a
  communicable disease related to an HCT/P if it
• 1. Is fatal
• 2. Is life-threatening
• 3. Results in permanent impairment of a body
  function or permanent damage to a body structure
  or
• 4. Necessitates medical or surgical
  intervention, including hospitalization

34
Eye Bank Reporting

• FDA defines an adverse reaction as a noxious and
  unintended response to any HCT/P for which there
  is a reasonable possibility that the HCT/P caused
  the response
• 21 CFR 1271.3(y)

35
Eye Bank Reporting

• FDA states that Communicable diseases include,
  but are not limited to those transmitted by
  viruses, bacteria, fungi, parasites, and TSE
  agents
• 21 CFR 1271.150(a)

36
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Response to Comment 1) We interpret
  reasonable possibility to mean that there is
  a possible causal relationship between an adverse
  experience and an HCT/P there are facts
  (evidence) or arguments to suggest a causal
  relationship.

37
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Response to Comment 11) We recognize that
  there may be situations in which there are
  multiple possible causes of a patients problem.
  Nevertheless, if one of the reasonable
  possibilities is that the HCT/P caused the
  problem, then this would meet the definition of
  adverse reaction. This would include
  situations in which the relationship between the
  response and the HCT/P is unlikely but
  nevertheless possible.

38
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Response to Comment 135) Problems not
  connected with communicable disease transmission
  are not required to be reported e.g., primary
  graft failure.

39
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Comment 137) One comment asked whether, if the
  investigation of a complaint points to a cause
  other than a failure of an eye banks good tissue
  practice, the eye bank is required to report
  these results.

40
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Response to Comment 137) If immediate
  investigation indicates that there is not a
  reasonable possibility of a relationship between
  an unintended and noxious response and the HCT/P,
  then the event is not considered an adverse
  reaction and you are not required to report it...

41
Eye Bank Reporting

• Clarifications regarding reporting to FDA in the
  preamble of CGTP
• (Response to Comment 139) ...we would generally
  consider that an infection at the site of a
  transplant would be reportable under 1271.350(a).

42
Eye Bank Reporting

• Draft CGTP Guidance, section XXXII A.
• Example 2 Endophthalmitis case A posterior
  chamber culture grows Staph epi. Although the
  eye bank did not culture the cornea prior to
  release, the surgeon performed a pre-implant
  culture, which was negative. The surgeon ordered
  additional antibiotics to treat the infection.

43
Eye Bank Reporting

• Draft CGTP Guidance, section XXXII A.
• Example 2 continued You must report this
  adverse reaction, even though the pre-implant
  culture was negative, because there is a
  reasonable possibility that the cornea caused
  this response, the adverse reaction involves a
  communicable disease, and it necessitated medical
  intervention.

44
Eye Bank Reporting

• Eye Bank Reporting to other establishments
• The source bank must notify all entities involved
  in the recovery, processing, storage, final
  distribution, tissue evaluation, and donor
  eligibility determination of the results of the
  investigation. Each of the involved entities must
  maintain documentation of the adverse event and
  results of the investigation forwarded to it by
  the source bank.
• EBAA Medical Standards G1.000

45
Eye Bank Reporting

• Eye Bank Reporting to other establishments
• Infection that the medical directors
  investigation determines to be reasonably likely
  to be of a systemic nature must be communicated
  to all entities that recovered organs or received
  or recovered tissues from that donor.
• EBAA Medical Standards G1.000

46
Summary

• Responsibilities under Joint Commission, EBAA,
  FDA
• End User
• Eye Bank

47
Questions?

• Amanda Nerone, QA Specialist
• Heartland Lions Eye Banks
• anerone_at_hleb.org